Special preventive measures: misoprostol in action potx

Section IV
Special preventive measures:
misoprostol in action
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‘With the emerging evidence on the use of various routes of administration of misoprostol,
particularly in the non-hospital setting, it is becoming clear that this drug should be available at
the community level in the hands of trained personnel, especially where oxytocin, Uniject and other
uterotonics are not present or practical for use.’
The Working Group of the Goa International Conference on the Prevention of
Post Partum Hemorrhage, July 15, 2006, Goa, India
16
MISOPROSTOL IN PRACTICE
M. Potts
Prior to the availability of misoprostol, it was
impossible to carry any significant element of
emergency obstetric care into homes where
women deliver without a skilled birth attendant.
As a low-cost, easy-to-administer, powerful
uterotonic with an excellent safety profile and
long shelf-life, misoprostol has a revolutionary
potential to reduce death and morbidity from
postpartum hemorrhage in precisely those situa-
tions where it is most common – delivery at
home without a skilled birth attendant.
In a placebo-controlled, community-based
trial in India, administration of 600 µg miso
-

prostol orally immediately after delivery sig
-
nificantly reduced postpartum hemorrhage (see
Addendum). Research in Indonesia, Nepal and
elsewhere is showing that community volun
-
teers with minimal training can teach illiterate
women to self-administer misoprostol effectively
and responsibly
1
(see Chapter 19). A 1000 µg
rectal dose of misoprostol can be used to treat
postpartum hemorrhage, in situations where an
appropriate technology exists to diagnose blood
loss (such as blood-soaked sarong or ‘kanga’),
and where births are attended by traditional
birth attendants (TBAs). In Tanzania, illiterate
TBAs, with a brief training, used misoprostol to
bring about a highly significant reduction in the
number of women who needed to be referred to
hospital or receive intravenous treatment
2
.
Although these measures may seem revolu-
tionary at first glance, they should be viewed as
an essential step towards a long-term strategy
where all women can be delivered by a certified
midwife or physician practicing active manage-
ment of the third stage of labor. Over the past
half-century, countries such as Sri Lanka and

Thailand have brought maternal mortality to
low levels by ensuring over 90% of deliveries are
attended by a skilled person able to use an
oxytocic, and ultimately all countries should
follow such a path.
Unfortunately, rapid population growth,
economic collapse and the spread of HIV/
AIDS in some African countries and the endless
recruitment of skilled health professions from
developing to developed countries will make the
road to providing comprehensive obstetric care
long and slow. During this interval, widespread
access to misoprostol and the education to use it
safely during home births have the potential to
make a significant contribution – perhaps even
the single most important contribution – to
reducing the global burden of deaths from
postpartum hemorrhage. The only other practi
-
cal intervention with the potential to reduce
postpartum hemorrhage in low-resource set
-
tings is realistic access to family planning, as all
women who wish to limit childbearing are at risk
of postpartum hemorrhage, and the older,
156
178
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higher-parity women, who have the greatest
unmet need for family planning, are at even
higher risk.
References
1. Wiknjosastro G, Sanghvi H. Preventing PPH
among women living in areas where a high
proportion of births are not attended by skilled
providers: Safety, acceptability, feasibility and
program effectiveness (SAFE) demonstration
project of community-based distribution of miso
-
prostol for prevention of PPH in rural Indonesia.
Proceedings of Preventing Postpartum Hemorrhage:
From Research to Practice, Bangkok, Thailand,
January 20–24, 2004:31–7
2. Prata N, Mbaruka G, Campbell M, Potts M,
Vahidnia F. Controlling postpartum hemorrhage
after home births in Tanzania. Int J Gynaecol
Obstet 2005;90:51–5
157
Misoprostol in practice
Editors’ Addendum
The Editors wish to bring the reader’s atten-
tion to the paper referred to by Professor
Potts on page 156. This paper has been pub-
lished in the October 7, 2006 issue of The
Lancet. To the Editors’ knowledge, this is the
largest placebo-controlled study of miso-
prostol for the prevention of postpartum

hemorrhage, and the results showed that
misoprostol significantly reduced the rate of
postpartum hemorrhage in the patients who
were administered this agent in comparison to
the patients who received the placebo control.
The full title of the paper and all authors
are:
R. J. Derman
1
, B. S. Kodkany
2
,S.S.
Goudar
2
, S. E. Geller
3
, V. A. Naik
2
,M.B.
Bellad
2
, S. S. Patted
2
, A. Patel
4
,S.A.
Edlavitch
1
, T. Hartwell
5

, H. Chakraborty
5
,
N. Moss
6
. Oral misoprostol in preventing post-
partum hemorrhage in a community setting.
1
University of Missouri-Kansas City School
of Medicine;
2
Jawaharlal Nehru Medical
College, Belgaum, Karnataka, India;
3
Univer-
sity of Illinois, Chicago College of Medicine,
USA;
4
John H. Stroger Jr. Hospital of Cook
County, USA;
5
Statistics and Epidemiology,
RTI International;
6
National Institute of
Child Health and Human Development.
179
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17
MANAGEMENT OF POSTPARTUM HEMORRHAGE AT THE
COMMUNITY LEVEL
N. Prata
The ability to manage postpartum hemorrhage
at the community level is an essential element in
any program to decrease maternal mortality
from postpartum hemorrhage
1
, as most of
the deliveries in developing countries occur at
home without the presence of a skilled birth
attendant
2
.
The efficacy, safety, and importance of miso
-
prostol use for postpartum hemorrhage man-
agement are well established for hospital-based
settings
3
. However, misoprostol’s most signifi-
cant impact will probably be at the household
level, where most deliveries occur. Some studies
have tested such technology in home births, and
all of them produced encouraging results.
During one intervention trial in rural Kigoma,
Tanzania, Prata and colleagues demonstrated
that traditional birth attendants (TBAs), who

assist in most home deliveries, were able to diag
-
nose postpartum hemorrhage and effectively
and safely administer 1000 µg of rectal miso
-
prostol to control postpartum hemorrhage
4
.
Blood loss measurement was standardized by
employing the traditional blood collection tool
used by women in the region – the local garment
that is colloquially referred to as a ‘kanga’
5
. This
study also showed that the ability to manage
postpartum hemorrhage in home births resulted
158
Intervention Non-intervention
Odds ratio
(95% CI)
Main outcomes of the study n % n %
PPH (blood loss ≥ 500 ml)
Referrals
111
8
24.5
1.8
73
75
18.5

19.0
1.3
0.1
(1.0–1.7)
(0.0–0.2)
Additional interventions among PPH cases n = 111 n =73
Type of additional interventions
a
Intravenous fluids
Blood transfusion
Manual removal of placenta
Repair of tears
Hysterectomy
Other medical interventions
d
b
1
b
1
1
0
0
0
0
0.9
0.9
0.9
0.0
0.0
0.0

0.0
c
69
c
25
16
17
4
1
7
94.5
34.3
21.9
23.3
5.5
1.4
9.6
a
Number of cases do not add up to total referred, some women had more than one intervention;
b
hospital
records not available for one patient; three patients did not need additional interventions; another three were
referred for other reasons than PPH;
c
hospital records not available for four patients; four patients did not
need additional interventions; two cases referred for other reasons than PPH;
d
medical interventions
included: Amoxyl tablets, methergin, and misoprostol.
Source: Prata N, et al. Controlling postpartum hemorrhage after home births in Tanzania. Int J Gynaecol

Obstet 2005;90:51–5
Ta bl e 1
Controlling postpartum hemorrhage (PPH) with a 1000 µg of misoprostol (intervention) in home
births, Kigoma, Tanzania
180
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in important reductions in the number of refer
-
rals and the need for additional interventions,
key factors in resource-poor settings (Table
1).This is particularly helpful in rural areas.
In settings where culturally appropriate
methods of measuring blood loss after delivery
are difficult to devise, all women could be
administered a prophylactic dose of 600 µg
misoprostol after delivery of the baby. Its safety
and efficacy in the hands of TBAs were shown
in a randomized, controlled trial in the Gam
-
bia
6
. In addition, in places where, for cultural or
other reasons, women deliver at home alone or
in the presence of a family member, self-admin
-
istration of a prophylactic dose of misoprostol,
distributed during pregnancy by trained com

-
munity health-care workers, are both viable
options that can produce promising results, as
was shown in other studies in Indonesia, Nepal,
and Afghanistan.
It will be many decades before all women in
low-resource settings can receive skilled atten-
tion at delivery in their homes. In the meantime,
misoprostol has the potential to make a signifi-
cant difference in reducing maternal mortality.
It should be made available for use in all settings
including home births, and particularly in those
where it must be self-administered.
References
1. Khan KS, Wojdyla D, Say L, Gulmezoglu AM,
Van Look PF. WHO analysis of causes of mater
-
nal death: a systematic review. Lancet 2006;367:
1066–74
2. AbouZahr C, Wardlaw T. Maternal mortality at
the end of a decade: signs of progress? Bull WHO
2001;79:561–8
3. Villar J, Gulmezoglu AM, Hofmeyr GJ, Forna F.
Systematic review of randomized controlled trials
of misoprostol to prevent postpartum hemor
-
rhage. Obstet Gynecol 2002;100:1301–12
4. Prata N, Mbaruku G, Campbell M, Potts M,
Vahidnia F. Controlling postpartum hemorrhage
after home births in Tanzania. Int J Gynaecol

Obstet 2005;90:51–5
5. Prata N, Mbaruku G, Campbell M. Using the
Kanga to measure postpartum blood loss. Int J
Gynaecol Obstet 2005;89:49–50
6. Walraven G, Blum J, Dampha Y, et al. Miso-
prostol in the management of the third stage of
labour in the home delivery setting in rural Gam-
bia: a randomised controlled trial. Br J Obstet
Gynaecol 2005;112:1277–83
159
Management at the community level
181
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18
ORAL MISOPROSTOL FOR PREVENTION OF POSTPARTUM
HEMORRHAGE BY PARAMEDICAL WORKERS IN INDIA
(AN ICMR TASK FORCE STUDY)
N. Chandhiok
Paramedical workers conduct deliveries in the
rural areas of India where active management of
the third stage of labor is not routinely practised
and uterotonic agents are only provided for the
management of postpartum bleeding. A multi-
site, cluster-randomized, feasibility study was
carried out to determine if paramedical workers
from rural Peripheral Health Centers (PHCs)
could actively manage the third stage of labor

using oral misoprostol to prevent postpartum
hemorrhage. Six hundred women each received
either active management of the third stage
of labor with 600 µg of oral misoprostol (inter
-
vention) or the current government guidelines
for prevention of postpartum hemorrhage
(controls). The primary outcome was blood loss
after delivery and this was measured using a
calibrated blood collection drape.
Baseline characteristics were comparable in
both groups and over 70% of women had
160
Intervention Comparison
Tablet
misoprostol
(n = 600)
Injection
methergine
(n = 531)
Tablet
methergine
(n = 58)
None
†
(n = 11)
Total
(n = 600)
Duration of third
stage of labor (min)

(mean ± SD)
7.9 ± 4.2 11.1 ± 4.1*** 9.6 ± 5.0*** 5.9 ± 2.4 10.9 ± 4.3***
Blood loss (ml)
Mean ± SD
Median
Q1–Q3
Range
Postpartum hemorrhage
139.7 ± 100.4
100
90–150
25–1300
4 (0.7)
211.8 ± 80.6***
200***
150–250
30–750
4 (0.8)
NS
211.6 ± 83.0***
200***
150–280
25–415
–
171.8 ± 178.3
100
100–160
100–700
1 (9.1)
211.0 ± 83.4***

200***
150–250
25–750
5 (0.8)
NS
Additional measures
Uterotonics
Intravenous fluids
Blood transfusion
Referred to higher level
of health facility for
PPH
4
4
1
2 (0.3)
2***
2***
–
1 (0.2)
–
–
–
1
1
–
1 (0.2)
3***
3***
–

2 (0.3)
***p < 0.001; **p < 0.01 when compared with the intervention;
†
group was not compared with intervention
due to small sample
NS
, not significant; PPH, postpartum hemorrhage
Ta bl e 1
Outcome of intervention. Figures in parentheses are percentages
182
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moderate anemia. The paramedical workers
were able to provide the intervention according
to the guidelines in almost all deliveries (99%).
There was a significant reduction in the dura
-
tion of the third stage of labor (7.9 ± 4.2 vs.
10.9 ± 4.3 min, p < 0.001), and the measured
blood loss after delivery in the intervention
group (139.7 ± 100.4 ml vs. 211.0 ± 83.4 ml,
p < 0.001). This magnitude of reduction is
significant for a country such as India where
80% of the women are anemic at the time of
delivery and any reduction in blood loss is
considered highly beneficial. The overall
incidence of postpartum hemorrhage observed
in the study was extremely low (< 1% in both

groups), and the study size was not adequate
to address the reduction in postpartum hemor
-
rhage at such low incidence (Table 1).
As most deliveries in rural areas take place at
home, there is a need to extend this study for all
domiciliary deliveries.
ACKNOWLEDGEMENT
This communication is based on the following
previously published article at the Editor’s
request: Chandhiok N, Dhillon BS, Datey S,
Mathur A, Saxena NC. Oral misoprostol for
prevention of postpartum hemorrhage by
paramedical workers in India. Int J Gynaecol
Obstet 2006;92:170–5
161
Prevention by paramedical workers in India
183
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19
OVERVIEW OF MISOPROSTOL STUDIES IN
POSTPARTUM HEMORRHAGE
A. Hemmerling
INTRODUCTION
These tables of peer-reviewed misoprostol
studies were compiled to provide the reader
with comprehensive references to the use of

misoprostol in practice since 1997, for both
prevention and treatment of postpartum hemor
-
rhage. The tables include both randomized and
non-randomized trials, and they represent a
diversity of situations. Table 1 provides an
overview of 32 studies in the prevention of
postpartum hemorrhage (including dosage
and route of administration). Table 2 gives an
overview of seven studies in the treatment of
postpartum hemorrhage (including dosage and
route of administration).
162
184
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163
Overview of misoprostol studies in postpartum hemorrhage
Authors Institutions Study title Journal n
Participants
in misoprostol
group
Dosage of
misoprostol
Route of
administration
Participants
in control

group(s)
Control agent(s)
Prata N,
Hamza S,
Gypson R, et al.
Bixby Program in
Population, Family
Planning and Maternal
Health, School of Public
Health, University of
California, Berkeley, USA
Misoprostol and active
management of the third
stage of labor
Int J Gynaecol
Obstet 2006
Jul 6 [epub
ahead of
print]
8 2532 1189 600 µg oral 1343 current AMTSL
practices
Nellore V,
Mittal S,
Dadhwal V
Dept. of Obstetrics and
Gynecology, All India
Institute of Medical
Sciences, Ansari Nagar,
New Delhi, India
Rectal misoprostol vs.

15-methyl prostaglandin
F
2α
for the prevention of PPH
Int J Gynaecol
Obstet 2006;
94:45–6
8 120 60 400 µg rectal 60 125 µg 15-methyl
prostaglandin F
2α
i.m.
Chandhiok N,
Dhillon BS,
Datey S, et al.
Division of Reproductive
Health and Nutrition,
Indian Council of Medical
Research, New Delhi, India
Oral misoprostol for
prevention of PPH by
paramedical workers in India
Int J Gynaecol
Obstet 2006;
92:170–5
8 1200 600 600 µg oral 600 current government
guidelines for PPH
prevention
Zachariah ES,
Naidu M,
Seshadri L

Dept. of Obstetrics and
Gynecology, Christian
Medical College Hospital
Vellore, India
Oral misoprostol in the third
stage of labor
Int J Gynaecol
Obstet 2006;
92:23–6
8 2023 730 400 µg oral [1] 617
[2] 676
[1] 10 IU oxytocin
i.m.
[2] 2 mg
ergometrine i.v.
Garg P,
Batra S,
Gandhi G
Maulana Azad Medical
College and Lok Nayak
Hospital,Delhi,India
Oral misoprostol vs. injectable
methylergometrine in
management of the third
stage of labor
Int J Gynaecol
Obstet 2005;
91:160–1
8 200 100 600 µg oral 100 0.2 mg
methylergometrine

i.v.
Ozkaya O,
Sezik M,
Kaya H, et al.
Dept. of Obstetrics and
Gynecology, School of
Medicine, Suleyman
Demirel University, Turkey
Placebo-controlled randomized
comparison of vaginal with
rectal misoprostol in the
prevention of PPH
JObstet
Gynaecol Res
2005;31:
389–93
8 150 [1] 50
[2] 50
400 µg [1] rectal
[2] oral
50 placebo
Hoj L,
Cardoso P,
Nielsen BB,
et al.
Dept. of Obstetrics and
Gynecology, Aarhus
University Hospital,
Denmark
Effect of sublingual

misoprostol on severe PPH
in a primary health center in
Guinea-Bissau: randomized
double-blind clinical trial
BMJ 2005;
331:723
8 661 330 600 µg sublingual 331 placebo
Continued
Ta bl e 1 Misoprostol for prevention
185
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164
POSTPARTUM HEMORRHAGE
Authors Institutions Study title Journal n
Participants
in misoprostol
group
Dosage of
misoprostol
Route of
administration
Participants
in control
group(s)
Control agent(s)
Walraven G,
Blum J,

Dampha Y,
et al.
Farafenni Field Station,
Medical Research
Council Laboratories,
Farafenni, Gambia
Misoprostol in the
management of the third stage
of labor in the home delivery
setting in rural Gambia: a
randomizedcontrolledtrial
BJOG 2005;
112:1277–83
8 1229 630 600 µg oral 599 2 mg ergometrine
oral
Vimala N,
Mittal S,
Kumar S,
et al.
Dept. of Obstetrics and
Gynecology, All India
Institute of Medical Sciences,
Ansari Nagar, New Delhi,
India
Sublingual misoprostol versus
methylergometrine for active
management of the third
stage of labor
Int J Gynaecol
Obstet 2004;

87:1–5
8 120 60 400 µg sublingual 60 0.2 mg
methylergometrine
i.v.
Lam H, Tang
OS, Lee CP,
et al.
Dept. of Obstetrics and
Gynecology, Queen Mary
Hospital,HongKongSAR,
China
A pilot-randomized
comparison of sublingual
misoprostol with syntometrine
on the blood loss in third stage
of labor
Acta Obstet
Gynecol Scand
2004;83:
647–50
8 60 30 600 µg sublingual 30 1 ml syntometrine
i.v. (5 IU
syntocinone and
0.5 mg ergometrine
maleate)
Caliskan E,
Dilbaz B,
Meydanli MM,
et al.
SSK Maternity and Women’s

Health Teaching Hospital,
Ankara, Turkey
Oral misoprostol for the third
stage of labor: a randomized
controlled trial
Obstet Gynecol
2003;101:
921–8
8 1574 388 600 µg oral [1] 404
[2] 384
[3] 398
[1] 600 µg
misoprostol plus
10 IU oxytocin i.v.
[2] 10 IU oxytocin
i.v.
[3] 10 IU oxytocin
i.v. plus 0.2 mg
methylergonovine
maleate
Oboro VO,
Tabowei TO
Maternity Unit, Zonal
General Hospital, Kwale,
Delta State, Nigeria
Arandomizedcontrolledtrial
of misoprostol vs. oxytocin in
the active management of the
third stage of labor
Obstet Gynecol

2003;23:
13–16
8 496 247 600 µg oral 249 10 IU oxytocin i.m.
Lumbiganon P,
Villar J, Piaggio
G, et al.
Dept. of Obstetrics and
Gynecology, Faculty of
Medicine, Khon Kaen
University, Thailand
Side-effects of oral
misoprostol during the first
24 h after administration in
thethirdstageoflabor
BJOG
2002;109:
1222–6
8 1686 843 600 µg oral 843 10 IU oxytocin i.m.
or i.v.
Ta bl e 1 Continued
186
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165
Overview of misoprostol studies in postpartum hemorrhage
Quiroga Diaz
R, Esparaza
Arechiga M,

Batiza Resendiz
V, et al.
Hospital de Ginecologia
y Obstetricia de Monterrey,
N. L. Mexico
Vaginal misoprostol in the
prevention of PPH
Ginecol Obstet
Mex 2002;70:
572–5
8 400 208 800 µg vaginal 192 current AMTSL
practices
Caliskan E,
Meydanli MM,
Dilbaz B, et al.
Social Security Council:
Maternity and Women’s
Health Teaching Hospital,
Kucukesat, Ankara, Turkey
Is rectal misoprostol really
effective in the treatment of
third stage of labor? A
randomizedcontrolledtrial
Am J Obstet
Gynecol 2002;
187:1038–45
8 1606 396 600 µg rectal [1] 401
[2] 407
[3] 402
[1] 10 IU oxytocin

i.v. plus 600 µg
misoprostol rectal
[2] 10 IU oxytocin
i.v.
[3] 10 IU oxytocin
i.v. plus 1 ml
methylergometrine
i.m.
Karkanis SG,
Caloia D,
Salenieks ME,
et al.
University of Toronto,
Toronto, Canada
Randomizedcontrolledtrial
of rectal misoprostol vs.
oxytocin in third stage
management
JObstet
Gynaecol Can
2002;24:
149–54
8 214 110 400 µg rectal 113 5 IU oxytocin i.v.
or 10 IU oxytocin
i.m.
Kundodyiwa
TW, Majoko F,
Rusakaniko S
Dept. of Obstetrics and
Gynecology, University

of Zimbabwe, Harare,
Zimbabwe
Misoprostol vs. oxytocin in
thethirdstageoflabor
Int J Gynaecol
Obstet 2001;
75:235–41
8 499 243 400 µg oral 256 10 IU oxytocin i.m.
Benchimol M,
Gondry J,
Mention JE,
et al.
Centre de Gynecologie
Obstetrique, Amiens,
France
Role of misoprostol in the
delivery outcome
J Gynecol
Obstet Biol
Reprod (Paris)
2001;30:
576–83
8 600 200 600 µg oral [1] 200
[2] 200
[1] 2.5 IU oxytocin
i.v.
[2] placebo
Gerstenfeld TS,
Wing DA
Women’s and Children’s

Hospital, Dept. of Obstetrics
and Gynecology, University
of Southern California Keck
School of Medicine, Los
Angeles, USA
Rectal misoprostol vs.
intravenous oxytocin for
the prevention of PPH after
vaginal delivery
Am J Obstet
Gynecol 2001;
185:878–82
8 325 159 400 µg rectal 166 20 IU oxytocin i.v.
Gulmezoglu
AM, Villar J,
Ngoc NT, et al.
WHO Collaborative Group
to Evaluate Misoprostol in
the Management of the
Third Stage of Labour
WHO multicenter randomized
trial of misoprostol in the
management of the third stage
of labor
Lancet 2001;
358:689–95
18 530 9264 600 µg oral 9266 10 IU oxytocin i.m.
or i.v.
Continued
187

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166
POSTPARTUM HEMORRHAGE
Authors Institutions Study title Journal n
Participants
in misoprostol
group
Dosage of
misoprostol
Route of
administration
Participants
in control
group(s)
Control agent(s)
Hofmeyr GJ,
Nikodem VC,
de Jager M,
et al.
Dept. of Obstetrics and
Gynecology, Coronation
Hospital and Effective Care
Research Unit, University
of the Witwatersrand,
Johannesburg, South Africa
Side-effects of oral
misoprostol in the third stage

of labor – a randomized
placebo-controlled trial
SAfrMedJ
2001;91:
432–5
8 600 300 600 µg oral 300 placebo
Bugalho A,
Daniel A,
Faundes A,
et al.
Maternity of the Hospital
Central de Maputo, Maputo,
Mozambique
Misoprostol for prevention of
PPH
Int J Gynaecol
Obstet 2001;
73:1–6
8 663 324 400 µg rectal 339 10 IU oxytocin i.m.
Ng PS, Chan
AS, Sin WK,
et al.
Dept. of Obstetrics and
Gynecology, The Chinese
University of Hong Kong,
Prince of Wales Hospital,
Shatin, New Territories
A multicenter randomized
controlled trial of oral
misoprostol and i.m

syntometrine in the
management of the third
stage of labor
Hum Reprod
2001;16:
31–5
8 2058 1026 600 µg oral 1032 1 ml syntometrine
i.v. (5 IU
syntocinone and
0.5 mg ergometrine
maleate 0.5 mg)
Walley RL,
Wilson JB,
Crane JM, et al.
Dept. of Obstetrics and
Gynaecology, St John’s,
Memorial University of
Newfoundland, Canada
A double-blind placebo
controlled randomized trial
of misoprostol and oxytocin in
the management of the third
stage of labor
BJOG 2000;
107:1111–15
8 401 203 400 µg oral 198 10 IU oxytocin i.m.
El-Refaey H,
Nooh R,
O’Brien P, et al.
Dept. of Obstetrics and

Gynaecology, University
College Hospital, London,
UK
The misoprostol third stage
of labor study: a randomized
controlled comparison between
orally administered misoprostol
and standard management
BJOG 2000;
107:1104–10
8 1000 501 500 µg oral 499 standard oxytocic
regimens (10 IU
oxytocin or 0.5 mg
ergometrine or
1 ml syntometrine)
Cook CM,
Spurrett B,
Murray H
Dept. of Obstetrics and
Gynaecology, University
of Sydney at Nepean
Hospital Penrith, New
South Wales, Australia
A randomized clinical trial
comparing oral misoprostol
with synthetic oxytocin or
syntometrine in the third
stage of labor
AustNZJ
Obstet

Gynaecol
1999;39:
414–19
8 863 424 400 µg oral 439 standard oxytocic
regimens (10 IU
oxytocin i.m. or
1mlsyntometrine
i.m.)
Ta bl e 1 Continued
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167
Overview of misoprostol studies in postpartum hemorrhage
Amant F, Spitz
B, Timmerman
D, et al.
Dept. of Obstetrics and
Gynaecology, University
Hospitals Leuven, Belgium
Misoprostol compared with
methylergometrine for the
prevention of PPH: a
double-blind randomized trial
Br J Obstet
Gynaecol
1999;106:
1066–70

8 200 100 600 µg oral 100 0.2 mg
methylergometrine
i.v.
Surbek DV,
Fehr PM,
Hosli I, et al.
Dept. of Obstetrics and
Gynecology, University
of Basel, Switzerland
Oral misoprostol for the third
stage of labor: a randomized
placebo-controlled trial
Obstet Gynecol
1999;94:
255–8
8 65 31 600 µg oral 34 placebo
Bamigboye AA,
Hofmeyr GJ,
Merrell DA
Dept. of Obstetrics and
Gynecology, Coronation
Hospital, and University of
the Witwatersrand,
Johannesburg, South Africa
Rectal misoprostol in the
prevention of PPH: a
placebo-controlled trial
Am J Obstet
Gynecol 1998;
179:1043–6

8 546 271 400 µg rectal 275 placebo
Hofmeyr GJ,
Nikodem VC,
de Jager M,
et al.
Dept. of Obstetrics and
Gynaecology, Coronation
Hospital and University of
the Witwatersrand,
Johannesburg, South Africa
A randomized placebo
controlled trial of oral
misoprostol in the third
stage of labor
Br J Obstet
Gynaecol
1998;105:
971–5
8 500 250 400 µg oral 250 placebo
Bamigboye AA,
Merrell DA,
Hofmeyr GJ,
et al.
Dept. of Obstetrics and
Gynecology, Natalspruit
Hospital and the University
of the Witwatersrand,
Johannesburg, South Africa
Randomizedcomparisonof
rectal misoprostol with

syntometrine for management
of third stage of labor
Acta Obstet
Gynecol Scand
1998;77:
178–81
8 491 241 400 µg rectal 250 1 ml syntometrine
i.m. (5 IU
syntocinone and
0.5 mg ergometrine
maleate 0.5 mg)
El-Refaey H,
O’Brien P,
Morafa W, et al.
Dept. of Obstetrics and
Gynaecology, University
College Hospital, London,
UK
Use of oral misoprostol in the
prevention of PPH
BJOG 1997;
104:336–9
8 237 237 600 µgoral 0–
PPH, postpartum hemorrhage
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POSTPARTUM HEMORRHAGE
Authors Institutions Study title Journal n
Participants
in misoprostol
group
Dosage of
misoprostol
Route of
administration
Participants
in control
group(s)
Control agent(s)
Prata N,
Mbaruku G,
Campbell M,
et al.
Bixby Population Program,
School of Public Health,
University of California,
Berkeley, USA
Controlling PPH after home
births in Tanzania
Int J Gynaecol
Obstet 2005;
90:51–5
849 454 1000 µg rectal 395 current practices
Walraven G,
Dampha Y,
Bittave B, et al.

Reproductive Health
Programme, Medical
Research Council
Laboratories, Farafenni,
The Gambia, South Africa
Misoprostol in the treatment
of PPH in addition to routine
management: a placebo
randomizedcontrolledtrial
BJOG 2004;
111:1014–17
160 79 600 µg 200 µgoral
and 400 µg
sublingual
81 placebo
Hofmeyr GJ,
Ferreira S,
Nikodem VC,
et al.
Effective Care Research
Unit, University of
Witwatersrand and Fort
Hare, and East London
Hospital Complex, East
London, South Africa
Misoprostol for treating PPH:
arandomizedcontrolledtrial
[ISRCTN72263357]
BMC
Pregnancy

Childbirth
2004;4:16
238 117 1000 µg 200 µgoral
and 400 µg
sublingual
and 400 µg
rectal
121 placebo
Shojai R,
Desbriere R,
Dhifallah S, et al.
Service de gynecologie-
obstetrique, CHU Nord,
Marseille, France
[Rectal misoprostol for PPH] Gynecol Obstet
Fertil 2004;
32:703–7
41 41 1000 µg rectal 0 –
Lokugamage
AU, Sullivan
KR, Niculescu
I, et al.
Dept. of Obstetrics &
Gynaecology, Royal Free
and University College
London School, London,
UK
A randomized study
comparing rectally
administered misoprostol

versus Syntometrine combined
with an oxytocin infusion for
the cessation of primary PPH
Acta Obstet
Gynecol Scand
2001;80:
835–9
64 32 800 µg rectal 32 1 ml syntometrine
i.m. (5 IU
syntocinone and
0.5 mg ergometrine
maleate) plus
10 IU oxytocin i.v.
Abdel-Aleem H,
El-Nashar I,
Abdel-Aleem A
Dept. of Obstetrics &
Gynecology, Faculty of
Medicine, Assiut University,
Assiut, Egypt
Management of severe PPH
with misoprostol
Int J Gynaecol
Obstet 2001;
72:75–6
18 18 600 µgor
1000
µg
rectal 0 –
O’Brien P,

El-Refaey H,
Gordon A, et al.
Dept. of Obstetrics and
Gynaecology, University
College Hospital,
London, UK
Rectally administered
misoprostol for the treatment
of PPH unresponsive to
oxytocin and ergometrine: a
descriptive study
Obstet Gynecol
1998;92:
212–14
14 14 1000 µg rectal 0 –
PPH, postpartum hemorrhage
Ta bl e 2
Misoprostol for treatment
190
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