UJIAN TENGAH SEMESTER (GASAL)

PARAFRASE JURNAL

Mata Kuliah :Metodologi Penelitian dan Biostatistik

Dosen Pengampu :Sulistyaningsih, S.KM.,MH.Kes

Oleh :
Dinayanti
1710104322

PROGRAM STUDI BIDAN PENDIDIK JENJANG DIPLOMA IV

FAKULTAS ILMU KESEHATAN
UNIVERSITAS AISYIYAH
YOGYAKARTA
2017

IDENTITAS JURNAL
International Journal of Gynecology and Obstetrics
Country Netherlands
Subject Area Medicine
and Category Obstetrics and Gynecology
Publisher
Publication
type
Elsevier BV
Journals
81
H Index
ISSN 00207292
Coverage 1973-ongoing
Scope The International Journal of Gynecology & Obstetrics publishes articles on all
aspects of basic and clinical research in the fields of obstetrics and gynecology and related
subjects, with emphasis on matters of worldwide interest. Features: Editorials; Articles;
Case Reports; Brief Communications; International Calendar; SOGC Clinical Practice
Guidelines; Review Articles; Contemporary Issues in Womens Health; Averting Maternal
Death and Disibility. New: Surgery and Technology. (source).

Category Year Quartile

Obstetrics and Gynecology 1997 Q2

Obstetrics and Gynecology 1998 Q2
Obstetrics and Gynecology 1999 Q2
Obstetrics and Gynecology 2000 Q2
Obstetrics and Gynecology 2001 Q2
Obstetrics and Gynecology 2002 Q2
Obstetrics and Gynecology 2003 Q2
Obstetrics and Gynecology 2004 Q2
Obstetrics and Gynecology 2005 Q2
Obstetrics and Gynecology 2006 Q2
Obstetrics and Gynecology 2007 Q2
Obstetrics and Gynecology 2008 Q2
Obstetrics and Gynecology 2009 Q1
Obstetrics and Gynecology 2010 Q2
Obstetrics and Gynecology 2011 Q1
Obstetrics and Gynecology 2012 Q2
Obstetrics and Gynecology 2013 Q2
Obstetrics and Gynecology 2014 Q2
Obstetrics and Gynecology 2015 Q2
Obstetrics and Gynecology 2016 Q2
 HASIL PARAFRASE

1. Abstrak
Penelitian ini bertujuan untuk menilai apakah penggunaan misoprostol dan oksitosin lebih baik dari
pada hanya menggunakan oksitosin dalam mengurangi perdarahan pervaginan pada wanita yang
mempunyai faktor risiko perdarahan postpartum (PPH).
Penelitian acak, tersamar ganda, menggunakan plasebo yang membandingkan,menggunakan
misoprostol 400 g atau tablet plasebo yang sesuai sublingually yang membandingkan 10 unit
oksitosin di sebuah perguruan tinggi kedokteran di India timur di kalangan wanita berusia minimal
18 tahun yang telah mengetahui faktor risiko tinggi untuk PPH.
Dari 144 peserta dimasukkan secara acak dalam setiap kelompok untuk mendapatkan misoprostol
pada 1 jam setelah melahirkan secara signifikan lebih rendah pada wanita yang menerima
misoprostol 400 g dibandingkan mereka yang menerima plasebo (225,8 156,7 mL vs 302,4
230,3 mL; P <0,001). Frekuensi PPH sedang (500-999 mL) secara signifikan lebih rendah pada
kelompok yang menerima misoprostol dibandingkan kelompok plasebo (5 [3,5%] vs 15 [10,4%]
peserta; P = 0,03).
Dibandingkan dengan oksitosin saja, misoprostol dengan oksitosin lebih efektif mengurangi
kehilangan darah setelah persalinan per vaginam pada wanita berisiko terkena PPH.
2. Pendahuluan
Perdarahan postpartum (PPH) adalah penyebab utama kematian ibu yang serius di negara-negara
berpenghasilan rendah. Sekitar 80% kematian maternal merupakan akibat meningkatnya komplikasi
selama kehamilan, persalinan dan setelah persalinan. Adapun faktor-faktor yang mempengaruhi
kejadian perdarahan postpartum adalah partus lama, peregangan uterus yang berlebihan,
multiparitas, pre-eklampsia berat, anemia, dan riwayat perdarahan postpartum sebelumnya.
Penggunaan obat uterotonik dalam bentuk oksitosin (10 IU intramus cularly) dalam waktu 1 menit
setelah kelahiran bayi baru lahir telah direkomendasikan oleh WHO sebagai komponen penting
AMTSL untuk alldeliveries. Misoprostol (600 g oral), turunan prostaglandin E1, telah
direkomendasikan sebagai obat uterotonik alternatif dalam pengaturan dimana oksitosin tidak
tersedia. Meskipun oksitosin memiliki tindakan cepat (dalam 3-7 menit injeksi intramuskular), efek
klinisnya hanya berlangsung sekitar 1 jam karena paruh pendeknya yang singkat 4-7 menit.
 Misoprostol, yang memiliki sifat menguntungkan (misalnya stabilitas pada suhu kamar, biaya
rendah, umur simpan yang panjang, dan rute administrasi non-parenteral), telah banyak dievaluasi
sebagai alternatif untuk oksitosin untuk profilaksis dan pengobatan PPH. Permulaan tindakannya
setelah pemberian sublingual - rute tercepat - sekitar 30 menit dan durasi tindakan tidak kurang dari
6 jam.Oksitosin dan misoprostol bekerja melalui reseptor oksitosin dan prostanoid, masing-masing,
di miometrium. Respon yang buruk terhadap satu uterotonik bisa terjadi karena variasi individu pada
populasi reseptor. Meskipun tindakan sinergis antara oksitosin dan misoprostol belum dilaporkan
sejauh ini, rejim uterotonik gabungan dapat dilakukan bermanfaat dengan memungkinkan
pemanfaatan maksimal reseptor yang tersedia.
Dosis dan efek samping terkait dosis dari uterotonik individu juga dapat dikurangi dengan kombinasi
pendekatan. Kombinasi misoprostol dan oksitosin telah dibandingkan dengan oksitosin saja untuk
profilaksis PPH di antara wanita yang menjalani persalinan sesar [11-14] dan vagina. pengiriman
[15-19]. Meskipun
wanita berisiko tinggi terkena PPH lebih mungkin mendapatkan keuntungan dari gabungan
uterotonik, hanya satu dari penelitian sebelumnya yang mencakup wanita highrisk secara
eksklusif.Oleh karena itu, bukti tidak sesuai dengan kebutuhan uterotonik untuk subset wanita
dengan faktor risiko PPH yang diketahui. Setiap intervensi yang dapat mengurangi risiko kehilangan
darah bagi wanita-wanita ini akan bermanfaat dari sudut pandang global dengan mencegah tidak
hanya kematian ibu tetapi juga morbiditas dalam hal intervensi bedah tambahan, transfusi darah, dan
anemia pascamelahirkan.
Dengan latar belakang ini, tujuan dari penelitian ini adalah untuk mengevaluasi apakah manajemen
aktif kala III dengan menggunakan misoprostol sublingual akan bermanfaat bagi perempuan yang
berisiko terkena PPH.

3. Metode
Penelitian prospektif acak dan double-blind saat ini dilakukan di Departemen Obstetri dan
Ginekologi, Nilratan Sircar Medical College and Hospital, Kolkata, India, sebuah rumah sakit
perawatan tersier di India timur. Studi ini melibatkan wanita berusia 18 tahun atau lebih yang
melahirkan secara vaginal antara tanggal 1 Oktober 2012, dan 31 Mei 2014.

4. Hasil
Selama masa studi, 750 wanita yang dirawat di bangsal pekerja disaring untuk mendapatkan
kelayakan. Secara keseluruhan, 364 memiliki satu atau lebih faktor risiko untuk PPH dan terdaftar
dalam penelitian ini. 288 wanita menjalani pengacakan dan menerima obat yang ditugaskan
Kedua kelompok memiliki demografi dan obstetri yang sama karakteristik (Tabel 1).
Berbagai faktor risiko untuk PPH diamati pada proporsi yang sama pada kedua kelompok (Tabel 2).
Kehilangan darah pascapersalinan pada 1 jam setelah persalinan secara signifikan lebih rendah di
antara wanita yang menerima misoprostol tambahan dengan oksitosin dibandingkan di antara mereka
yang menerima oksitosin saja (Pb0. 001) (Tabel 3).
Jumlah kehilangan darah pada awalnya dibagi menjadi tiga kategori (b 500 mL, 500-999 mL,
dan1000 mL). Namun, kehilangan darah kurang dari 500 mL untuk kebanyakan wanita di kedua
kelompok; Hasilnya, kategori pertama terbagi menjadi dua (b150 mL dan 150-499 mL).
Persentase wanita yang secara signifikan lebih besar pada misoprostol tambahan hilang kurang dari
150 mL darah dibandingkan dengan wanita dengan oksitosin saja (Pb0.001) (Tabel 3).
Kejadian PPH sedang (500-999 mL) juga signifikan lebih rendah pada kelompok yang menerima
misoprostol tambahan dibandingkan pada kelompok yang menerima plasebo (P = 0,03) (Tabel 3).
Namun, tidak ada perbedaan yang signifikan dalam kejadian PPH berat (1000 mL) antara kedua
kelompok (Tabel 3).
 Penurunan perdarahan postpartum rata-rata pada hemoglobin secara signifikan lebih rendah di antara
wanita yang menerima misoprostol tambahan dengan oksitosin dibandingkan di antara mereka yang
menerima oksitosin saja (P = 0,004) (Tabel 4).
Pada (Tabel 4) juga diamati bahwa lebih banyak wanita dalam kelompok uterotonik gabungan
mengalami penurunan perdarahan postpartum dalam hemoglobin kurang dari 5 g / L (Pb0.001).
Obat uterotonik tambahan dan transfusi darah diperlukan sedikit lebih sedikit untuk wanita yang
menerima misoprostol tambahan daripada mereka yang menerima plasebo, walaupun perbedaannya
tidak signifikan (Tabel 4)
Seorang wanita di setiap kelompok memerlukan intervensi bedah untuk PPH yang sulit diobati.
Pemindahan plasenta secara manual diperlukan untuk dua wanita yang menerima oksitosin saja.
Tidak ada kematian maternal yang terjadi. Menggigil adalah efek samping yang paling umum, dan
terjadi secara signifikan lebih sering di antara wanita yang diberi misoprostol tambahan (Pb0.001)
(Tabel 5). Meskipun pyrexia lebih sering terjadi pada kelompok misoprostol tambahan dibandingkan
kelompok plasebo, perbedaannya tidak signifikan (P = 0,1) (Tabel 5).

5. Pebahasan
Di antara kohort wanita saat ini yang diketahui faktor risikonya PPH, pemberian plus oksitosin
dikurangi postpartum kehilangan darah selama periode observasi 1 jam dan menurunkan insidensi
PPH sedang dibandingkan dengan oksitosin saja. Tidak ada perbedaan yang signifikan yang diamati
pada kejadian PPH berat (1000 mL) atau kebutuhan untuk obat uterotonik tambahan dan transfusi
darah. Uji coba acak secara acak yang sebelumnya membandingkan oksitosin ditambah misoprostol
dengan oksitosin saja untuk pencegahan PPH setelah pemberian vagina, dua diantaranya mirip
dengan penelitian ini dalam hal dosis dan rute misoprostol [18,19], sedangkan dua penelitian di
Turki [15,16] dan satu di Nigeria[17] berbeda dalam dosis dan rute pemberian, juga pada obat yang
diberikan pada kelompok kontrol
Kehilangan darah dengan kombinasi misoprostol dan oksitositik rutin dibandingkan dengan oksitosin
saja diamati oleh Hofmeyr et al. [18] (189 mL vs 199 mL; perbedaan rata-rata-9,58 mL, CI 95%, -
22,3 sampai 3,1) dan Fawole et al. [19] (211,8 mL vs 217,5 mL; perbedaan rata-rata-5,7 mL, 95%
CI-16,0 sampai 27,4). Namun, pengurangannya kecil dan tidak signifikan dalam kedua penelitian.
Perbedaan antara penelitian saat ini dan penyelidikan sebelumnya dalam hal ukuran pengurangan
kehilangan darah dapat disebabkan oleh faktor-faktor berikut: pertama, dua penelitian sebelumnya
mencakup perempuan dengan multipel berisiko rendah; dan kedua, ukuran sampel pada penelitian
sebelumnya lebih besar dari kelompok sekarang. Ada kemungkinan bahwa menambahkan
misoprostol ke oksitosin rutin mungkin menguntungkan wanita dengan faktor risiko tinggi untuk
PPH sampai tingkat yang lebih tinggi, seperti yang diamati dalam penelitian ini.
Meskipun termasuk perempuan dengan faktor risiko tinggi untuk PPH,
Badejoko dkk tidak menunjukkan penurunan kehilangan darah dengan penggunaan misoprostol
tambahan (387,28 203,09 mL vs 386,73 298,51 mL, P = 0,07). Pencurian mereka mungkin
disebabkan oleh fakta bahwa misoprostol tambahan dibandingkan dengan infus oksitosin intravena
tambahan, berbeda dengan penelitian ini, yang dikontrol plasebo.
 Pengamatan terhadap kejadian PPH (500-999 mL) secara signifikan lebih rendah di antara wanita
yang diberi misoprostol tambahan konsisten dengan hasil meta analisis dari empat percobaan
sebelumnya.
4013 wanita, risiko relatif 0,75, 95% CI 0,58-0,96). Penelitian saat ini, bersama dengan sebagian
besar penyelidikan sebelumnya [15,16,18,19], mengamati tidak ada perbedaan yang signifikan antara
kelompok kejadian PPH berat (1000 mL) atau kebutuhan untuk obat oksitosik tambahan dan
transfusi darah. Kombinasi misoprostol dan oksitosin juga terbukti efektif dalam mengurangi
kehilangan darah pada kisaran 500-999 mL tanpa mempengaruhi kejadian PPH utama (1000 mL)
dalam percobaan serupa pada wanita yang menjalani persalinan cesar.
Meskipun populasi berisiko tinggi, rata-rata dan kerugian median darah yang tercatat pada kedua
kelompok penelitian ini rendah dibandingkan dengan penelitian sebelumnya terhadap wanita
berisiko tinggi. Perbedaan ini mungkin muncul secara kebetulan, tergantung pada populasi aspecific
yang diambil sampelnya selama periode tempuhnya.
Penurunan kadar hemoglobin postpartum yang lebih kecil pada kelompok yang menerima
misoprostol tambahan terbukti dalam penelitian ini, konsisten dengan hasil penelitian di Nigeria.
PercobaanTurkish gagal menunjukkan adanya perbedaan yang signifikan dalam penurunan
hemoglobin postpartum. Penggunaan tambahan oxytocin dan transfusi darah adalah dua faktor yang
mempengaruhi penurunan hemoglobin.Variabilitas dalam kriteria pemberian uterotonik
tambahan,Transfusi darah mungkin mengakibatkan konflik ini terkait dengan penurunan
hemoglobin. Dalam penelitian ini, jumlah wanita yang secara signifikan lebih tinggi pada kelompok
misoprostol tambahan mencatat penurunan hemoglobin kurang dari 5 g / L dibandingkan dengan
wanita yang diberi oksitosin saja. Ini menunjukkan bahwa ada kemungkinan efek menguntungkan
dari rezim gabungan dalam mencegah anemia pascamelahirkan Saat ini, bagaimanapun, tidak ada
data komparatif tersedia dan pengamatan ini harus diverifikasi dalam penelitian lebih lanjut.
Kematian ibu atau morbiditas utama tidak diamati pada kedua kelompok
dalam penelitian ini, konsisten dengan pengamatan sebelumnya.

6. Kesimpulan
Dibandingkan dengan oksitosin saja, misoprostol dengan oksitosin lebih efektif mengurangi
kehilangan darah setelah persalinan per vaginam pada wanita berisiko terkena perdarahan
postpartum PPH. Menambahkan 400 g misoprostol sublingual standar 10 IU oksitosin
intramuskular untuk penanganan rutin tahap ketiga pada wanita dengan faktor risiko tinggi yang
diketahui untuk PPH tampaknya lebih efektif daripada oksitosin saja dalam mengurangi perdarahan
postpartum.
IJG-08500; No of Pages 5
International Journal of Gynecology and Obstetrics xxx (2015) xxxxxx

Contents lists available at ScienceDirect

International Journal of Gynecology and Obstetrics

journalhomepage:www.elsevier.com/locate/ijgo

CLINICAL ARTICLE

A randomized trial of sublingual misoprostol to augment routine third-

stage management among women at risk of postpartum hemorrhage

Picklu Chaudhuri , Arindam Majumdar

Department of Obstetrics and Gynecology, Nilratan Sircar Medical College, West Bengal University Of Health Sciences, Kolkata, India

article info abstract

Article history: Objective: To assess whether a combination of misoprostol and oxytocin is more beneficial than oxytocin alone in reducing
Received 15 March 2015 blood loss after vaginal delivery among women with known risk factors for postpartum hemorrhage (PPH). Methods: A
Received in revised form 18 June 2015 randomized, double-blind trial was conducted in a medical college in eastern India among women aged at least 18 years who
Accepted 20 October 2015 had known high-risk factors for PPH. Using a computer-generated random number sequence (block size 68), participants
were randomly assigned to receive 400 g misoprostol or matched placebo tablets sublingually, in addition to 10 units of
Keywords:
oxytocin, after vaginal delivery. The primary outcomes were postpartum blood loss at 1 hour and frequency of PPH. Analyses
Adjunct
were by intention to treat. Results: Both groups contained 144 participants. Postpartum blood loss at 1 hour after delivery was
Blood loss
Misoprostol significantly lower among women who received misoprostol than among those who received placebo (225.8 156.7 mL vs
Oxytocin 302.4 230.3 mL; P b 0.001). The frequency of moderate PPH (500999 mL) was significantly lower in the group receiving
Postpartum hemorrhage misoprostol than in the placebo group (5 [3.5%] vs 15 [10.4%] participants; P = 0.03). Conclusion: As compared with
oxytocin alone, misoprostol with oxytocin more effectively reduced blood loss after vaginal deliv-ery among women at risk of
PPH.

Clinical Trial Registry India: CTRI/2014/03/004491

2015 International Federation of Gynecology and Obstetrics. Published by Elsevier Ireland Ltd. All rights reserved.

1. Introduction
Postpartum hemorrhage (PPH) is the single major cause of maternal
mortality and serious maternal morbidity in low-income countries [1]. Most
cases of PPH (almost 80%) occur because the uterus fails to con-tract [2], and
might be avoided by anticipation of risk factors, active management of the
third stage of labor (AMTSL), and prompt interven-tion. Multiple pregnancy,
polyhydramnios, grand multiparity, severe pre-eclampsia, prepartum
hemorrhage, prolonged and obstructed labor, augmented labor, obesity,
anemia, and known previous PPH are some of the risk factors for atonic PPH
[3].
The use of uterotonic drugs in the form of oxytocin (10 IU intramus-
cularly) within 1 minute of delivery of the newborn has been recom-mended
by WHO as an essential component of AMTSL for all deliveries [4].
Misoprostol (600 g orally), a prostaglandin E1 derivative, has been
recommended as the alternative uterotonic drug in settings where oxytocin is
unavailable [5]. However, a meta-analysis [6] found that PPH still occurs
even after administration of the gold standard
Corresponding author at: Department of Obstetrics and Gynecology, Nilratan Sircar
Medical College, 138 AJC Bose Road, Sealdah, Kolkata, 700014, West Bengal, India. Tel.: +91
9432277443; fax: +91 03322658179.
E-mail address: picklu.chaudhuri@gmail.com (P. Chaudhuri).
first line oxytocic. This finding could be important for women with one or
more of the risk factors for PPH. Although oxytocin has a rapid onset of
action (within 37 minutes of intramuscular injection), its clin-ical effect lasts
for only approximately 1 hour owing to its short half-life of 47 minutes [7].
Misoprostol, which has beneficial properties (e.g. stability at room
temperature, low cost, long shelf-life, and non-parenteral routes of ad-
ministration), has been widely evaluated as an alternative to oxytocin for
prophylaxis and treatment of PPH [8]. Its onset of action after sublin-gual
administrationthe quickest of all routesis about 30 minutes and its
duration of action is not less than 6 hours [9,10].
Oxytocin and misoprostol act through oxytocin and prostanoid re-ceptors,
respectively, in the myometrium. Poor response to one uterotonic could be
due to individual variation in the receptor popula-tion. Although a synergistic
action between oxytocin and misoprostol has not been reported so far, a
combined uterotonic regime could be beneficial by enabling maximum
utilization of the available receptors. The dose and the dose-related adverse
effects of an individual uterotonic might also be reduced with a combined
approach.
The combination of misoprostol and oxytocin has been compared with
oxytocin alone for PPH prophylaxis among women undergoing both cesarean
delivery [1114] and vaginal delivery [1519]. Although women at high risk
of PPH are more likely to benefit from the combined uterotonics, only one of
the previous studies included exclusively high-

http://dx.doi.org/10.1016/j.ijgo.2015.06.064
0020-7292/ 2015 International Federation of Gynecology and Obstetrics. Published by Elsevier Ireland Ltd. All rights reserved.

Please cite this article as: Chaudhuri P, Majumdar A, A randomized trial of sublingual misoprostol to augment routine third-stage management among women
at risk of postpartum hemorrhage, Int J Gynecol Obstet (2015), http://dx.doi.org/10.1016/j.ijgo.2015.06.064
2 P. Chaudhuri, A. Majumdar / International Journal of Gynecology and Obstetrics xxx (2015) xxxxxx
risk women [17]. Evidence is therefore lacking with respect to require-ment
of uterotonics for the subset of women with known risk factors for PPH. Any
intervention that would lessen the risk of blood loss for these women would
be beneficial from the global point of view by averting not only maternal
death but also morbidity in terms of additional surgi-cal intervention, blood
transfusion, and postpartum anemia.
Against this background, the aim of the present study was to evalu-ate
whether augmentation of routine third-stage management with sublingual
misoprostol would be beneficial for women at risk of PPH.
2. Materials and methods
The present prospective, randomized, double-blind study was con-ducted
in the Department of Obstetrics and Gynaecology, Nilratan Sircar Medical
College and Hospital, Kolkata, India, a tertiary-care teaching hospital in
eastern India. The study included women aged 18 years or older who
delivered vaginally between October 1, 2012, and May 31, 2014, and who
had one or more of the following known risk factors for PPH: multiple
pregnancy; polyhydramnios; induced and augmented labor; prolonged labor,
defined in accordance with standard guidelines via a partogram; obesity,
defined as a body mass index (BMI, calculated as weight in kilograms divided
by the square of height in meters) above 30; grand multiparty (4); severe
pre-eclampsia or eclampsia; anemia, defined as a hemoglobin level less than
80 g/L; and known previous PPH. The study excluded women who had
cesarean delivery or instru-mental vaginal delivery; known hypersensitivity to
misoprostol and/ or oxytocin; major cardiovascular, hepatic, or hematologic
disorders; or intrauterine fetal death or stillbirth. The protocol was approved
by the Institutional Ethical Committee and was registered with Clinical Trial
Registry India (Registration No. CTRI/2014/03/004491). All partic-ipants in
the study provided written informed consent.
On admission to the labor ward, women were screened for eligibility by
interview, clinical examination, and review of recent investigations. Those
who fulfilled the selection criteria were approached for participa-tion during
the first stage of labor and consent was obtained. Labor was monitored by
partogram, and women who needed augmentation of labor or had prolonged
labor were also enrolled on providing consent.
When delivery was imminent with crowning of the presenting fetal part,
each participant was randomized by computer-generated random number
sequence and block randomization (blocks of 68) to receive either two 200-
g tablets of misoprostol (Zitotec; Sun Pharmaceutical Industries Ltd,
Mumbai, India) or two tablets of placebo (with the same color, size, and
shape) using sealed, opaque, and sequentially numbered packets.
Randomization and maintenance of confidential re-cords were done by
residents who were not involved in the trial. Prep-aration of the sealed
packets, allocation, and administration of the drugs were done by the labor
room midwife. Participants, investigators, and data analysts were masked to
group assignment.
All deliveries were conducted by residents. The packets were opened and
misoprostol/placebo was administered sublingually within 1 minute of
delivery of the newborn (or second newborn in the case of twins) by the labor
room midwife. Simultaneously, each participant re-ceived 10 IU of
intramuscular oxytocin (Syntocinon; Novartis India Ltd, Mumbai, India).
Additional oxytocic drugs were administered on the basis of clinical
judgement by the senior resident. Blood transfusions were given to women
who were hemodynamically unstable and/or had a postpartum hemoglobin
concentration of less than 60 g/L, in line with the hospital protocol.
Linens soaked with amniotic fluid were removed soon after delivery of the
newborn, and a pre-weighed thick cotton pad with plastic lining was placed
under the buttocks. All blood clots were removed from the vagina and kept in
a plastic bag. The pad was replaced if completely soaked during the 1-hour
observation period. Episiotomies were repaired immediately after complete
delivery of the placenta, and cotton swabs used during this procedure were
not included in the blood loss as-sessment. The difference in weight between
the soaked and dry pad was
Please cite this article as: Chaudhuri P, Majumdar A, A randomized trial of sublingual misoprostol to augment routine third-stage management among women
at risk of postpartum hemorrhage, Int J Gynecol Obstet (2015), http://dx.doi.org/10.1016/j.ijgo.2015.06.064
added to the weight of blood clots to calculate the total blood loss (1 mL was
considered equal to 1 g given the specific gravity of blood of 1.08).
Vital signs were recorded every 15 minutes. Hemoglobin was mea-sured
before delivery and 24 hours after delivery.
The primary outcomes were the measured postpartum blood loss (from
delivery of the newborn to 1 hour after delivery) and the incidence of PPH.
The secondary outcomes were postpartum drop in he-moglobin (24 hours
after delivery), requirement of additional oxytocic (1 hour), need for blood
transfusion (before discharge), additional sur-gical intervention for PPH (24
hours), maternal complications (before discharge), and adverse effects related
to the uterotonic (1 hour).
A power calculation was used to determine the sample size. In a pre-vious
study, mean postpartum blood loss among women with high-risk factors
receiving oxytocin after vaginal delivery was 386 298 mL [17]. Under the
assumption that administration of misoprostol would reduce blood loss by
100 mL, 140 women would be required in each group to have a 80% chance
of detecting a significant difference at the 5% level. Under the further
assumption of approximately 5% loss during follow-up, participants were
enrolled until there were a few more than 140 in each group.
Analysis was done by intention to treat. Excel version 7 (Microsoft,
Redmond, WA, USA) and MedCalc version 11 (MedCalc Software, Ostend,
Belgium) were used for statistical analyses. Results were report-ed as mean
SD, number (percentage), and median (range). Student t, MannWhitney U,
2
, and Fisher exact tests were performed to compare variables. Mean and
median differences with 95% confidence intervals (CIs) and relative risks
with 95% CIs were calculated for outcome param-eters as appropriate. P b
0.05 was considered statistically significant.
3. Results
During the study period, 750 women admitted to the labor ward were
screened for eligibility. In total, 364 had one or more risk factors for PPH and
were enrolled in the study. A further 78 women, who were initially screened
and found to be ineligible because of a lack of risk factor, were subsequently
enrolled because they needed augmenta-tion of labor or showed evidence of
prolonged labor. After exclusion of 154 women, 288 women underwent
randomization and received the assigned drug (Fig. 1).
The two groups had similar baseline demographic and obstetric
characteristics (Table 1). The various risk factors for PPH were observed in
similar proportions in the two groups (Table 2).
Mean postpartum blood loss at 1 hour after delivery was signifi-cantly
lower among women who received adjunct misoprostol with oxytocin than
among those who received oxytocin alone (P b 0.001) (Table 3). The amount
of blood loss was initially divided into three categories (b500 mL, 500999
mL, and 1000 mL). However, blood loss was less than 500 mL for most
women in both groups; as the result, the first category was subdivided into
two (b150 mL and 150499 mL). A significantly greater proportion of
women on adjunct misoprostol lost less than 150 mL of blood as compared
with women on oxytocin alone (P b 0.001) (Table 3). The incidence of
moderate PPH (500999 mL) was also significantly lower in the group
receiving adjunct misoprostol than in the group receiving placebo (P = 0.03)
(Table 3). However, there was no significant difference in the incidence of
severe PPH (1000 mL) between the two groups (Table 3).
The mean postpartum drop in hemoglobin was significantly lower among
women who received adjunct misoprostol with oxytocin than among those
who received oxytocin alone (P = 0.004) (Table 4). It was also observed that
more women in the combined uterotonic group had a postpartum drop in
hemoglobin of less than 5 g/L (P b 0.001) (Table 4). Additional uterotonic
drugs and blood transfusion were re-quired slightly less frequently for women
who received adjunct miso-prostol than for those who received placebo,
although the differences were not significant (Table 4).
 P. Chaudhuri, A. Majumdar / International Journal of Gynecology and Obstetrics xxx (2015) xxxxxx 3

Patients assessed for eligibility

(n=750)

Excluded (n=386)

1 risk factor for PPH (n=364)

Needed augmentation of labor or
had prolonged labor (n=78)

Eligible for inclusion (n=442)

Excluded (n=154)
Coagulopathy (n=4)
HELLP syndrome (n=6)
Cesarean delivery (n=108)
Instrumental delivery (n=26)
Declined to participate (n=10)

Randomization (n=288)

Allocated to and received misoprostol Allocated to and received placebo

(n=144) (n=144)

Fig. 1. Flow of participants through the study. Abbreviations: PPH, postpartum hemorrhage; HELLP, hemolysis, elevated liver enzymes, low platelet count.

One woman in each group required surgical intervention for intrac-table difference was observed in the incidence severe PPH (1000 mL) or the
PPH. Manual removal of placenta was needed for two women who received requirement for additional uterotonic drugs and blood transfusion.
oxytocin alone. No maternal death occurred. Of five randomized trials that previously compared oxytocin plus
Shivering was the most common adverse effect, and it occurred signif- misoprostol with oxytocin alone for prevention of PPH after vaginal de-
icantly more often among women given adjunct misoprostol (P b 0.001) livery, two were similar to the present study in terms of the dose and route of
(Table 5). Although pyrexia was more frequent in the adjunct misopros-tol misoprostol [18,19], whereas two studies in Turkey [15,16] and one in
group in than in the placebo group, the difference was not significant (P = 0.1) Nigeria [17] differed in dose and route of administration, as well as in the
(Table 5). drug administered in the control group.
In agreement with the present findings, a trend toward a reduction in blood
loss with combined use of misoprostol and routine oxytocic as compared with
4. Discussion oxytocic alone was observed by Hofmeyr et al. [18] (189 mL vs 199 mL;
mean difference 9.58 mL, 95% CI, 22.3 to 3.1) and Fawole et al. [19]
Among the present cohort of women with known risk factors for PPH, (211.8 mL vs 217.5 mL; mean difference
administration of misoprostol plus oxytocin reduced postpartum blood loss 5.7 mL, 95% CI 16.0 to 27.4). However, the reduction was small and
during a 1-hour observation period and decreased the inci-dence of moderate insignificant in both studies. The discrepancy between the present study and
PPH as compared with oxytocin alone. No significant the previous investigations in terms of the size of the reduc-tion in blood loss
could be due to the following factors: first, the
Table 1
a
Demographic and obstetric characteristics of the study patients.
Table 2
Characteristic Misoprostol group Placebo group P value a,b
Risk factors.
(n = 144) (n = 144)
b Risk factor Misoprostol group Placebo group P value
Age, y 24.7 4.1 25.3 4.2 0.2
b (n = 144) (n = 144)
Parity 0 (05) 1 (05) 0.5
c c
Primipara 77 (53.5) 64 (44.4) 0.2 Multiple pregnancy 23 (16.0) 27 (18.8) 0.6
d c
Grand multipara (4) 8 (5.6) 5 (3.5) 0.6 Polyhydramnios 6 (4.2) 09 (6.3) 0.6
b c
Length of pregnancy, wk 37.8 0.9 37.5 1.4 0.1 Severe pre-eclampsia or eclampsia 40 (27.8) 46 (32.0) 0.5
b c
BMI 25.3 4.5 24.7 4.1 0.2 Anemia (hemoglobin b80 g/L) 11 (7.6) 9 (6.3) 0.8
b c
Birth weight, kg 2.7 0.4 2.8 0.4 0.2 Prolonged labor 18 (12.5) 12 (8.3) 0.3
b c
Preoperative hemoglobin, g/L 111.9 17.9 113.3 15.1 0.5 Labor augmented by oxytocin 43 (29.9) 49 (34.0) 0.5
c c
1 risk factor 125 (86.8) 118 (81.9) 0.3 Obesity (BMI N30) 13 (9.0) 10 (7.0) 0.7
c d
2 risk factors 19 (13.2) 26 (18.1) 0.3 Grandmultiparity (4) 8 (5.6) 5 (3.5) 0.6
c d
Episiotomy/perineal tear 87 (60.4) 94 (65.2) 0.5 Known previous PPH 5 (3.5) 9 (6.3) 0.4
Abbreviation: BMI, body mass index (calculated as weight in kilograms divided by the square Abbreviations: BMI, body mass index (calculated as weight in kilograms divided by the square
of height in meters). of height in meters); PPH, postpartum hemorrhage.
a a
Values are given as mean SD, median (range), or number (percentage), unless in-dicated Values are given as number (percentage) unless indicated otherwise.
otherwise. b
b
The total number of risk factors in each group was more than the total number of women in
By t test. each group because some women had more than one risk factor.
c 2 c 2
By test. By test.
d d
By Fisher exact test. By Fisher exact test.

Please cite this article as: Chaudhuri P, Majumdar A, A randomized trial of sublingual misoprostol to augment routine third-stage management among women
at risk of postpartum hemorrhage, Int J Gynecol Obstet (2015), http://dx.doi.org/10.1016/j.ijgo.2015.06.064
4 P. Chaudhuri, A. Majumdar / International Journal of Gynecology and Obstetrics xxx (2015) xxxxxx

Table 3 Table 5
a a
Primary outcomes. Adverse effects.

Outcome Misoprostol Placebo Difference P value Adverse effect Misoprostol Placebo group Relative risk P value
group group or RR group (n = 144) (n = 144) (95% CI)
(n = 144) (n = 144) (95% CI) b
Shivering 39 (27.1) 6 (4.2) 6.5 (2.814.9) b0.001
c
Postpartum blood loss, mL Pyrexia (N38 C) 8 (5.6) 2 (1.4) 4.0 (0.918.5) 0.1
b c
Mean SD 225.8 156.7 302.4 230.3 76.6 (30.9122.3) b0.001 Nausea/vomiting 2 (1.4) 0 5.0 (0.2103.2) 0.5
c
Median (range) 200 (1201250) 220 (1451500) 20.0 (2.337.7) Diarrhea 2 (1.4) 0 5.0 (0.2103.2) 0.5
Blood loss, mL
c Abbreviation: CI, confidence interval.
b150 25 (17.4) 1 (0.7) 25.0 (3.4182.1) b0.001 a
150499 112 (77.8) 124 (86.1) 0.9 (0.81.0) 0.09 c b
Values are given as number (percentage) unless indicated otherwise.
2
d
500999 5 (3.5) 15 (10.4) 0.3 (0.10.9) 0.03 c By test.
d
1000 2 (1.4) 4 (2.8) 0.5 (0.12.7) 0.7 By Fisher exact test.
Abbreviations: RR, relative risk; CI, confidence interval.
a
Values are given as number (percentage) unless indicated otherwise. A significantly smaller postpartum drop in hemoglobin concentration in
b
By MannWhitney U test.
c 2 the group that received adjunct misoprostol was evident in present study,
By test.
d
By Fisher exact test.
consistent with the results of the Nigerian study [17]. The Turkish trials,
however, failed to show any significant difference in the postpar-tum drop in
hemoglobin [15,16]. Use of additional oxytocic and blood transfusion are the
two factors that affect the drop in hemoglobin. Variability in the criteria for
previous two studies included low-risk multiparous women; and sec-ond, the administering additional uterotonics and blood transfusion might have
sample size in the previous studies was larger than the present cohort. It is resulted in these conflicting findings relat-ed to the drop in hemoglobin.
possible that adding misoprostol to routine oxytocin might benefit women
with high-risk factors for PPH to a greater extent, as ob-served in the present In the present study, a significantly higher number of women in the
study. adjunct misoprostol group recorded a drop in hemoglobin of less than 5 g/L as
Although they included women with high-risk factors for PPH, Badejoko compared with women given oxytocin alone. This indicates that there is a
et al. [17] did not show any reduction in blood loss with the use of additional possible beneficial effect of the combined regime in preventing postpartum
misoprostol (387.28 203.09 mL vs 386.73 298.51 mL, P = 0.07). Their anemia. At present, however, there are no comparative data available and this
finding might be a result of the fact that additional misoprostol was compared observation should be verified in further studies.
with additional intrave-nous oxytocin infusion, by contrast with the present Maternal death or major morbidity was not observed in either group in the
study, which was placebo-controlled. present study, consistent with previous observations [1519]. Shivering and
pyrexia were the two most common adverse effects after the administration of
The present observation of a significantly lower incidence of PPH (500 misoprostol, again in accordance with similar pre-vious studies [1519].
999 mL) among women given adjunct misoprostol was consistent with the These adverse effects were, however, self-limiting.
results of a meta-analysis [18] of four previous trials (4013 women; relative The strength of the present study lies in the exclusive inclusion of women
risk 0.75, 95% CI 0.580.96). The present study, along with most previous at high risk of PPH. A limitation was the application of the gravi-metric
investigations [15,16,18,19], observed no signif-icant difference between the method of blood loss assessment, which is less accurate than other methods.
groups in the incidence of severe PPH (1000 mL) or the requirement for
additional oxytocic drugs and blood transfusion. The combination of In conclusion, adding 400 g of sublingual misoprostol to the stan-dard
misoprostol and oxytocin was also found to be effective in reducing blood regime of 10 IU of intramuscular oxytocin for routine third-stage
loss in the range 500999 mL without affecting the incidence of major PPH management of women with known high-risk factors for PPH seems to be
(1000 mL) in a similar trial of women undergoing cesarean delivery [11]. more effective than does oxytocin alone in reducing both postpar-tum blood
loss and the incidence of moderate PPH (500999 mL). Future research with
Despite the high-risk population, the mean and median blood losses larger cohorts is required in this area.
recorded in both groups of the present study were low in comparison with a
previous study of high-risk women [17]. This difference might have arisen by
Conflict of interest
chance, being dependent on a specific population sam-pled over a fixed period
of time.
The authors have no conflicts of interest.

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Table 4
a
Secondary outcomes. [1] Khan KS, Wojdyla D, Say L, Gulmezoglu AM, Van Look PF. WHO analysis of causes of
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b5 16 (11.1) 1 (0.7) 16.0 (2.2119.1) b0.001 haemorrhage. Geneva: World Health Organization; 2007.
c
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Values are given as number (percentage) unless indicated otherwise. Karoshi M, editors. A Textbook of Postpartum Haemorrhage. London: Sapiens
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By test. [8] Hofmeyr JG, Gulmezoglu AM. Misoprostol for the prevention and treatment of
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at risk of postpartum hemorrhage, Int J Gynecol Obstet (2015), http://dx.doi.org/10.1016/j.ijgo.2015.06.064
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JUDUL
FAKTOR-FAKTOR YANG MEMPENGARUHI KEJADIAN
PERDARAHAN POSTPARTUM
OUTLINE TINJAUAN TEORI
A. TEORI
1. Perdarahan Postpartum
a. Definisi
b. Klasifikasi Perdarahan Postpartum
c. Gejala klinis Perdarahan Postpartum
d. Kondisi patologis yang menimbulkan perdarahan postpartum
e. Faktor-Faktor Mempengaruhi Perdarahan Postpartum
f. Komplikasi perdarahan postpartum
2. Tinjauan Islam
B. KERANGKA KONSEP
C. HIPOTESIS

Kerangka Konsep

Variabel Independen/Variabel Bebas Variabel Dependen

Faktor yang Mempengaruhi

Perdarahan postpartum
1. Umur Perdarahan Postpartum
2. Paritas
3. Jarak Persalinan
4. Partus lama
5. Peregangan uterus yang
berlebihan 1. Atonia uteri

6. Riwyat HPP 2. Laserasi jalan lahir

7. Anemia 3. Retensio plasenta

8. Riwayat SC 4. Sisa plasenta

5. Inversion uteri
6. kelainan pembekuan

:Area yang diteliti darah

Gambar 2 Kerangka Konsep Penelitian

 Perdarahan postpartum adalah perdarahan lebih dari 500 cc yang terjadi setelah bayi lahir
pervaginam atau lebih dari 1000 cc setelah persalinan abdominal dalam 24 jam dan sebeleum 6 minggu
setelah persalinan. Berdasarkan waktu terjadinya perdarahan postpartum dapat dibagi menjadi
perdarahan primer dan perdarahan sekunder. Adapun faktor-faktor yang mempengaruhi kejadian
perdarahan postpartum adalah Umur, paritas, partus lama, jarak kehamilan kurang dari dua tahun,
peregangan uterus yang berlebihan, oksitosin drip, anemia, dan persalinan dengan tindakan.

Devinisi Operasional Penelitian

Definisi operasional yaitu ruang lingkup untuk membatasi variabel- variabel yang diamati atau
teliti (Notoatmodjo, 2009).
N Nama Defini Cara ukur Alat Hasil ukur Skala
O Variabel Operasional ukur Ukur

1 Perdarahan adalah perdarahan Penelusuran Formulir 1. Perdarahan Nomin

Postpartum lebih dari 500 cc informasi isian 2. Tidak al
yang terjadi rekam medis perdarahan
setelah bayi lahir
pervaginam atau
lebih dari 1000 cc
setelah persalinan
abdominal

2 Umur Umur ibu yang Penelusuran Formulir 1. Tidak Nomin

tercata saat masuk informasi isian berisiko: 20- al
rumah sakit untuk rekam medis 35 tahun
mendapat 2. Berisiko: <20
pelayanan tahun atau <
35 tahun
3 Paritas Jumlah seluruh Penelusuran Formulir 1. Primipara Ordinal
persalinan yang informasi isian 2. Multipara
dialami ibu rekam medis 3. Grandemultif
ara
4 Jarak Waktu sejak Penelusuran Formulir 1. Jarak Nomin
persalinan kelahiran informasi isian persalinan al
sebelumnya rekam medis beresiko
sampai terjadinya 2. Jarak
kelahiran persalinan
berikutnya. tidak berisiko

5 Partus lama Penelusuran Formulir 1. Partus lama Nomin

informasi isian 2. Partus tidak al
rekam medis lama

6 Peregangan Jumlah seluruh Penelusuran Formulir 1. Peregangan Nomin

uterus yang persalinan yang informasi isian uterus al
berlebihan dialami ibu rekam medis berlebihan
2. Peregangan
uterus tidak
berlebihan

7 Riwayat Jumlah seluruh Penelusuran Formulir 1. Ada riwayat Nomin

HPP persalinan yang informasi isian HPP al
dialami ibu rekam medis 2. Tidak ada
riwayat HPP
8 Anemia Jumlah seluruh Penelusuran Formulir 1. Anemia Nomin
persalinan yang informasi isian Hb <11gr al
dialami ibu rekam medis %
2. Tidak
Anemia
Hb 11
gr%

9 Riwayat Penelusuran Formulir 1. Ada riwayat Nomin

SC informasi isian SC al
rekam medis 2. Tidak ada
riwayat SC