Middle East Fertility Society Journal (2014) 19, 812

Middle East Fertility Society

Middle East Fertility Society Journal

www.mefsjournal.org
www.sciencedirect.com

OPINION ARTICLE

Is the Time of administration of misoprostol

of value? The uterotonic eect of misoprostol given
pre- and post-operative after elective cesarean
section
Ahmed H. Abd-Ellah, Abdel Aziz E. Tamam, Mostafa Mohammed Khodry

Department of Obstetrics & Gynecology, Faculty of Medicine, South Valley University, Qena, Egypt
Received 13 June 2013; accepted 22 September 2013
Available online 22 October 2013

KEYWORDS
Cesarean section;
Misoprostol;
Blood loss;
Uterotonic drugs;
Pre-operative;
Post-operative

Abstract Objective: The aim of the current study was to compare blood loss in pre- and postoperatively rectally administered 600 lg of misoprostol in elective cesarean delivery, in order to
determine the optimal time for drug administration (CS).
Study design: A 30-month prospective, single-blind, randomized, clinical trial was done in the
Qena University Hospital, Egypt, from January 2010 to October, 2012.
Methods: Intervention consisted of pre and post-operative rectally administered misoprostol. At
baseline, there were no signicant differences in the demographic and obstetric variable between
groups. Primary outcome measures were differences in intra-operative and postoperative blood loss
between groups. Secondary outcomes measures were hemoglobin levels pre and operative (24 h
after CS) and the need for additional uterotonic drugs.
Results: A total of 300 subjects were enrolled (pre-operative administrated rectally misoprostol
n = 150, post-operative administrated rectally misoprostol n = 150). Subjects receiving pre-operative misoprostol achieved signicantly lower blood loss compared to those receiving post-operative
misoprostol (620 291 ml vs. 898 321 ml, p < 0.05), respectively. The need for additional uterotonic was signicantly higher in subjects receiving post-operative misoprostol compared to those
receiving pre-operative misoprostol (53.3% vs. 30%, p, 0.05), respectively.
Conclusion: Pre-operative rectally administrated misoprostol appears to be more effective than
post-operative rectally administrated misoprostol in reducing blood loss, and in decreasing the need
for other uterotonic drugs in cesarean section delivery.
2013 Production and hosting by Elsevier B.V. on behalf of Middle East Fertility Society.

* Corresponding author. Tel.: +20 1007088098.

E-mail address: khodrymesh@yahoo.com (M.M. Khodry).
Peer review under responsibility of Middle East Fertility Society.

Production and hosting by Elsevier

1. Introduction
Cesarean section is one of the most commonly performed
major operations in women throughout the world. Postpartum
hemorrhage (PPH) is dened as a blood loss of more than

1110-5690 2013 Production and hosting by Elsevier B.V. on behalf of Middle East Fertility Society.
http://dx.doi.org/10.1016/j.mefs.2013.09.002

Is the Time of administration of misoprostol of value? The uterotonic effect of misoprostol given
1000 ml in the rst 24 h. following cesarean section. Postpartum hemorrhage (PPH) is the leading cause of maternal mortality worldwide, and the number of maternal deaths due to
postpartum hemorrhage is estimated to exceed 100,000 maternal deaths each year (1). Misoprostol is a synthetic PGE1 analogue, owing to its uterotonic properties; it is now one of the
most popular drugs in obstetrics (2). The low cost of drug,
safety, stability, and the ease of administration through multiple routes make it a good option in poor setting and in patients
who are vomiting or under anesthesia (3). The drug was
proved to be effective in reducing blood loss when administered orally, buccally and rectally in many previous studies
(4,5). However, the optimal time of drug administration has
not been addressed in these previous studies. The current study
was set to compare blood loss in pre- and post-operatively rectally administered 600 lg of misoprostol in elective cesarean
delivery, in order to determine the optimal time for drug
administration.
2. Materials and methods
This is a prospective, randomized; single-blind controlled clinical study was conducted at the department of Obstetrics &
Gynecology, Qena University Hospital from January 2010 to
October, 2012. The study was approved by the Ethics Committee of Qena University Hospital, Egypt. The total number of
elective CS during the study period was 358. Of these; 305 women met the inclusion criteria who were randomly allocated
into two groups by using computer generated tables. Group
1, women receiving pre-operatively rectally administered
600 lg of misoprostol (n = 153) and Group 2, women receiving post-operative 600 lg of misoprostol (n = 152). Three women were lost to follow-up in group 1, and 2 women were lost
to follow-up in the group 2 and nally 300 women were enrolled (150 subjects in each group) in both groups (Figure 1).
2.1. Inclusion criteria
Patients included in the study were those not in active labor,
had reactive non-stress test, had no hypersensitivity or contraindications to prostaglandins, and had no history of
coagulopathy.
2.2. Exclusion criteria
The reasons for exclusion were placenta previa, maternal
hypertension, diabetes mellitus and previous CS and those
with active labor. Patients who met the inclusion criteria were
subjected to clinical evaluation, and laboratory investigations
such as complete blood picture, urine analysis, blood sugar
and coagulation prole (including prothrombin time, and partial thromboplastin time). Sonographic evaluation was offered
to all study subjects with special emphasis on placental localization, estimated of the expected date of delivery and biophysical prole. Group 1, included 153 patients who received
600 lg misoprostol rectally after spinal anesthesia and urinary
bladder catheterization (3 tablets each 200 lg) and Group 1 included 152 patients who received 600 lg misoprostol rectally
postoperatively on the operating theater (3 tablets each
200 lg). Cesarean section delivery was done under spinal anesthesia by senior obstetricians who were blind to allocation. The

placenta was delivered by cord clamping and uterine compression. The uterus was closed in situ in continuous unlocked suture in 2 layers using Vicryl 1 suture (Johnson & Johnson,
USA). The peritoneum and muscle was closed by Vicryl 0 suture. The sheath was closed by Vicryl 1, and the skin was
closed by subcutical suture using proline double zero suture
in both groups. Estimation of blood loss was started after skin
incision. A dedicated nurse was responsible for collection of
blood and amniotic uid in two separate suction sets and
weighting surgical towels before and after the operation. Post
partum blood loss during the rst 24 h after the operation was
assessed by weighting soaked napkins. Preoperative hemoglobin was measured 2 h before surgery and assessed 24 h after
the operation. The neonatal outcome including; Apgar score,
the need for neonatal intensive care unit (NICU) admission
and neonatal death were assessed in the two groups. The drug
side effects as regards post operative fever, vomiting and shivering were compared in both groups. Data were collected and
tabulated and statistically analyzed by IBM computer using
the Statistical Package for the Social Sciences (SPSS version
15). Chi-square test was used to compare qualitative variables
between groups and Fisher exact test was used instead of Chisquare test when the expected cell count is less than 5. Student
t-test was used to compare the quantitative variables in parametric data. p value < 0.05 was set signicant.
3. Results
There were no signicance differences between both groups as
regards age, parity, body mass index, and gestational age, and
preoperative hemoglobin level (Table 1). The mean blood loss
during and after CS delivery was signicantly lower in the preoperatively rectally administered misoprostol group
(620 291) when compared to the post-operative rectally
administered misoprostol group (898 321) and this difference was statistically signicant with p value < 0.05. The need
for additional uterotonic was signicantly higher in the preoperatively rectally administered misoprostol group than the
post-operative rectally administered misoprostol group
(53.3% vs. 30%, p < 0.05), respectively (Table 2). Postoperative hemoglobin level (24 h) was signicant lower in the postoperative
rectally
administered
misoprostol
group,
(9.8 1.24) than the pre-operatively rectally administered
misoprostol group (10.5 1.31) with p value 0.034. However,
the change in Hb level between the preoperative level and post
operative level was obviously higher in the post-operative rectally administered misoprostol group (1.9 0.45) than the
pre-operatively rectally administered misoprostol group
(1.2 0.67) (p = 0.032). The neonatal outcomes and drug
side effects were nearly comparable in both groups as regards
the Apgar score at 1 and 5 min, need for neonatal intensive
care admission, post operative fever, shivering and vomiting
in both groups (Table 3).
4. Discussion
Prophylactic administration of misoprostol rectally after cesarean delivery is increasing nowadays to decrease blood loss
after CS delivery. To the best of our knowledge, this is the rst
study that compares preoperative and post-operative rectally
administrated misoprostol in reducing blood loss at cesarean

10

A.H. Abd-Ellah et al.

Total number of elecve CS
(n=358)
"Excluded (n =53)

Did not meet inclusion

criteria (n=43)
Refused parcipaon (n=10)

Consented to parcipate
(n=305)

Randomizaon

Allocated to Pre-operave rectally administrated

misoprostol

Allocated to post-operave rectally

administrated misoprostol

Lost to flow-up

Lost to ow-up (n=3)

(n=2)

Analyzed (n=150)

Figure 1

Table 1

Analyzed (n=150)

Flow chart of the study design.

Patients characteristics of the study groups.

Age (years)
Parity
Body mass index
Gestational age
Preoperative Hb level

Study group (N = 150)

Control group (N = 150)

p value

24.7 4
3.20 1.1
21 0.8
39.4 0.8
11.8 3.6

25.08 3.9
3.5 1.9
22 0.6
39.1 0.9
11.6 4.8

0.542
0.461
0.442
0.58
0.48

Values presented by mean SD, p value < 0.05 was set be signicant.

section. Reduction of operative blood loss at cesarean section

is benecial to patients in terms of decreased postoperative
morbidity and a decrease in risks associated with blood transfusions (6). Misoprostol, a PGE1 analogue, has been investigated both for prevention and management of PPH due to
its uterotonic effect. However, there is no general consensus
on the optimal time, dose or route of administration (7). Rectally administered misoprostol has the advantage of a slower
absorption rate, lower concentration level and consequently
lower adverse effects (8) compared to Sublingual misoprostol,
which has the greatest bioavailability among all routes of
administration and a higher incidence of complications (6).
On the other hand, oral route has the highest side effects
(8,9). For these reasons, the rectal route was the preferred
route of administration in the present study. The current study
used 600 lg of misoprostol which was administered rectally in

both groups after catheter insertion and before draping to allow time for absorption and action to occur. Because we are
comparing the optimal time for misoprostol administration,
other uterotonic drugs were instituted when intra-operative
or post-operative bleeding exceeded 500 ml. In the current
study, the mean blood loss during and after CS delivery was
signicantly lower in the pre-operative rectally administered
misoprostol group compared to those receiving misoprostol
post-operatively. This can be explained by the fact that, high
availability and higher concentration of misoprostol had occurred after the end of the surgical procedure, hence leading
to strong uterine contraction and consequently resulted in
the reduction of blood lost. Further study is warranted to
determine the concentration of misoprostol in the blood in
both groups following the end of the procedure. A randomized
controlled trial using 400 lg was conducted to evaluate the im-

Is the Time of administration of misoprostol of value? The uterotonic effect of misoprostol given
Table 2

11

Primary outcome measures in the two studied groups.

Characteristics

Study group (n = 150)

Control group (N = 150)

p value

Blood loss ML
Need for uterotonic drug
No need
Need
Mean Hb level((g/dl)
Postoperative 24 h
Change in Hb

620 291

898 321

0.003

105 (70)
45 (30)

70 (46.7)
80 (53.3)

0.023

10.5 1.31
1.2 0.67

9.8 1.24
1.9 0.45

p < 0.05
0.032

Values are presented as (Mean SD), number (percentage), p value < 0.05 was set be signicant.

Table 3

Fetal and drug adverse effect in both groups.

Apgar score at 5 min

Meconium aspiration
NICU admission
Pyrexia
Shivering
Vomiting

Study group (N = 100)

Control group (N = 100)

p value

9.74 0.66
8 0.42
7 0.31
15 (15%)
20 (20%)
7 (7%)

9.88 0.60
6 0.56
7 0.42
17 (17%)
18 (18%)
11 (11%)

>0.05
>0.05
>0.05
>0.05
>0.05
>0.05

pact of preoperative administration of rectal misoprostol on

blood loss among 400 women undergoing elective cesarean
delivery and concluded that, preoperative treatment with
400 lg rectal misoprostol signicantly reduced blood loss
(10). Most of the relevant studies supported the view that rectally administered misoprostol is better than other uterotonic
drugs in reducing blood loss specially if administered rectally
(11). In the present study, post-operative Hb level (after
24 h) was signicantly lower in the post-operative rectally
administered misoprostol (9.8 1.24 g/dl) than pre-operatively administered group (10.5 1.31 g/dl), p < 0.05. This
nding agrees with results obtained by Elsedeek who concluded that, pre-operative rectally administered misoprostol
after elective CS resulted in a signicantly higher Hb level
and hematocrit values in rectally administered misoprostol
than placebo (10). Pre-operative misoprostol was used via oral
(12) and sublingual routes for different operations for blood
reduction which was reported to be effective in reducing blood
loss during surgery (13).
The additional need for other uterotonic drugs to control
blood loss during CS delivery was markedly noticed in women
who received post-operative misoprostol (n = 80, 53.3%)
compared to women who received pre-operative misoprostol
(n = 4530%), p < 0.05 respectively. Again, this nding is in
agreement with the results of Elseedeek (10) who mention in
their studies that the percentage of women requiring additional
oxytocics was signicantly higher in the control group than in
the study group (10). Jennifer et al., 2005, reported the same
ndings however, in their study they used the buccal route,
not the rectal route for drug administration (11). In this study,
there was no clinically signicant difference in the neonatal
outcomes in both groups as regards the timing of administration of the drug and this agrees with the results obtained by
Elsedeek (10) who reported that the preoperative administration of the misoprostol rectally did not cause any fetal adverse
effects in the study group.

5. Conclusion
Pre-operative rectally administrated misoprostol appears to be
more effective than post-operative rectally administrated misoprostol in reducing blood loss, and in decreasing the need for
other uterotonic drugs in cesarean section delivery.
Conict of interest
We declare no conict of interest.
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