JOURNAL

( T R EAT MENT )

Victor J. Guerrero

SUBLINGUAL MISOPROSTOL VERSUS

INTRAMUSCULAR OXYTOCIN
FOR PREVENTION OF POSTPARTUM
HEMORRHAGE IN UGANDA: A
DOUBLE-BLIND RANDOMIZED NONINFERIORITY TRIAL
Esther C. Atukunda1* , Mark J. Siedner2 , Celestino Obua3 , Godfrey R. Mugyenyi1 ,
Marc Twagirumukiza4 , Amon G. Agaba1
1 Mbarara University of Science and Technology, Mbarara, Uganda,
2 Department of Medicine, Massachusetts General Hospital, Boston, Massachusetts, United States of America,
3 Department of Pharmacology and Therapeutics, School of Biomedical Sciences, College of Health Sciences, Makerere University,
Kampala, Uganda,
4 Department of Pharmacology, Faculty of Medicine and Health Sciences, Ghent University, Ghent, Belgium

PLOS Medicine November 2014 | Volume 11 | Issue 11 | e1001752

BACKGROUND OF THE STUDY

Postpartum hemorrhage (PPH) is a leading cause of
maternal death in sub-Saharan Africa. Although the World Health
Organization (WHO) recommends use of oxytocin for
prevention of PPH, misoprostol use is increasingly common
owing to advantages in shelf life and potential for sublingual
administration. There is a lack of data about the comparative
efficacy of oxytocin and sublingual misoprostol, particularly at the
recommended dose of 600 mg, for prevention of PPH during
active management of labor.

Atukunda et al. (2014) Misoprostol versus Oxytocin for Prevention of Postpartum Hemorrhage

SIGNIFICANCE OF THE STUDY

The data will contribute to the comparative efficacy of
oxytocin and sublingual misoprostol for prevention of
PPH during active management of labor.
This data will contribute to a complex array of data on
optimal prevention of PPH in the third stage of labor in
resource-limited settings.

Atukunda et al. (2014) Misoprostol versus Oxytocin for Prevention of Postpartum Hemorrhage

DEFINITION OF TERMS
Oxytocin
a hormone that stimulates uterine contractions and limits uterine bleeding after
birth, is the standard of care for prevention of PPH during the third stage of labor.
Use is limited by a number of factors including a perceived requirement for
administration by skilled personnel, cold chain storage, and a requirement for
sterile syringes and needles.
Dose given: 10 IU

Misoprostol
a synthetic prostaglandin with uterotonic properties, has been proposed as an
alternative strategy for prevention of PPH in settings where oxytocin use is not
feasible.
Administered sublingually, enabling a more rapid onset of action and greater
bioavailability by avoiding first-pass metabolism
Dose given: 600ug
Atukunda et al. (2014) Misoprostol versus Oxytocin for Prevention of Postpartum Hemorrhage

DEFINITION OF TERMS

Postpartum Hemorrhage
loss of more than 500 ml of blood within 24 hours of delivery
Severe Postpartum Hemorrhage
loss of more than 1000 ml of blood within 24 hours of delivery

Atukunda et al. (2014) Misoprostol versus Oxytocin for Prevention of Postpartum Hemorrhage

METHODS
This is a double-blind, double-dummy randomized
controlled non-inferiority trial between 23 September 2012
and 9 September 2013 at Mbarara Regional Referral Hospital in
Uganda
1,140 women were randomized to receive 600 ug of
misoprostol sublingually or 10 IU of oxytocin intramuscularly,
along with matching placebos for the treatment they did not
receive.
570 participants are included in each group. The list was
shared only with the study clinical pharmacist, who prepared
the study drugs and placebos.
Atukunda et al. (2014) Misoprostol versus Oxytocin for Prevention of Postpartum Hemorrhage

Atukunda et al. (2014) Misoprostol versus Oxytocin for Prevention of Postpartum Hemorrhage

DELIVERY

Blood loss was measured over the first 24 hours

after delivery

ANALYSIS OF RESULTS

Atukunda et al. (2014) Misoprostol versus Oxytocin for Prevention of Postpartum Hemorrhage

RESULTS
Postpartum hemorrhage
MISOPROSTOL
28.6%
(N=163)

OXYTOCIN
17.4%
(N=99)

Relative risk [RR] 1.64, 95% CI 1.32 to 2.05, p<0.001; absolute risk difference 11.2%, 95% CI 6.44 to 16.1

Atukunda et al. (2014) Misoprostol versus Oxytocin for Prevention of Postpartum Hemorrhage

RESULTS
Severe Postpartum Hemorrhage
MISOPROSTOL
3.6%
(N=20)

OXYTOCIN
2.7%
(N=15)

RR 1.33, 95% CI 0.69 to 2.58, p = 0.391; absolute risk difference 0.9%, 95% CI -1.12 to 2.88.

Atukunda et al. (2014) Misoprostol versus Oxytocin for Prevention of Postpartum Hemorrhage

RESULTS
Mean Blood Loss
2h
24h

MISOPROSTOL

OXYTOCIN

p-value

341.5 ml
484.7 ml

304.2 ml
432.8 ml

p=0.002
p=0.001

Interpretation: On average, women given misoprostol had lost slightly more

blood by 2h and 24 hours after delivery than those given oxytocin.

Atukunda et al. (2014) Misoprostol versus Oxytocin for Prevention of Postpartum Hemorrhage

RESULTS
Side Effects (shivering and fever)
Women in the misoprostol group more
commonly experienced shivering (RR 1.91, 95%
CI 1.65 to 2.21, p<0.001) and fever (RR 5.20,
95% CI 3.15 to 7.21, p = 0.005)

Atukunda et al. (2014) Misoprostol versus Oxytocin for Prevention of Postpartum Hemorrhage

CONCLUSION
Sublingual Misoprostol 600 mg is inferior to oxytocin
10 IU for prevention of primary PPH in women undergoing
uncomplicated vaginal deliveries.
The researchers found a 64% increased risk of primary
PPH (measured blood loss >/= 500 ml at 24 h) and an
absolute risk increase of 11.2% with misoprostol versus
oxytocin.
The researchers also found a 33% higher rate of severe PPH
(measured blood loss >1,000 ml) in the misoprostol group,
although this difference was not statistically significant
Atukunda et al. (2014) Misoprostol versus Oxytocin for Prevention of Postpartum Hemorrhage

CONCLUSION
The study found no significant differences in rate of severe
PPH, need for blood transfusion, postpartum hemoglobin,
change in hemoglobin, or use of additional uterotonics
between study groups.
Preliminary data that sublingual misoprostol at a dose of 600
mg is likely to be of important benefit where oxytocin is
unavailable.
The data therefore signal that, among relatively healthy women
undergoing uncomplicated labor, oxytocin provides modest
benefit over sublingual misoprostol for prevention of PPH
generally, and should be the preferred agent where
feasible and available.
Atukunda et al. (2014) Misoprostol versus Oxytocin for Prevention of Postpartum Hemorrhage

THANK YOU

v.1.1

Atukunda et al. (2014) Misoprostol versus Oxytocin for Prevention of Postpartum Hemorrhage