Pharmacologic intervention for retained placenta: a systematic review and meta-analysis.

Background
The primary objective of postpartum haemorrhage (PPH) prevention and treatment is to reduce maternal deaths. Misoprostol has the major public health advantage over injectable medication that it can more easily be distributed at community level. Because misoprostol might have adverse effects unrelated to blood loss which might impact on mortality or severe morbidity, it is important to continue surveillance of all relevant evidence from randomised trials. This is particularly important as misoprostol is being introduced on a large scale for PPH prevention in low-income countries, and is commonly used for PPH treatment in well-resourced settings as well.

Objectives
To review maternal deaths and severe morbidity in all randomised trials of misoprostol for prevention or treatment of PPH.

Search methods
We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (11 January 2013).

Selection criteria
We included randomised trials including pregnant women who received misoprostol in the postpartum period, versus placebo/no treatment or other uterotonics for prevention or treatment of PPH, and reporting on maternal death, severe morbidity or pyrexia.

We planned to include cluster- and quasi-randomised trials in the analysis, as a very large number of women will be needed to obtain robust estimates of maternal mortality but we did not identify any for this version of the review. In future updates of this review we will include trials reported only as abstracts if sufficient information is available from the abstract or from the authors.

Data collection and analysis
Two review authors independently assessed trials for inclusion and extracted data.

Main results
We included 78 studies (59,216 women) and excluded 34 studies.There was no statistically significant difference in maternal mortality for misoprostol compared with control groups overall (31 studies; 11/19,715 versus 4/20,076 deaths; risk ratio (RR) 2.08, 95% confidence interval (CI) 0.82 to 5.28); or for the trials of misoprostol versus placebo: 10 studies, 6/4626 versus 1/4707 ; RR 2.70; 95% CI 0.72 to 10.11; or for misoprostol versus other uterotonics: 21 studies, 5/15,089 versus 3/15,369 (19/100,000); RR 1.54; 95% CI 0.40 to 5.92. All 11 deaths in the misoprostol arms occurred in studies of misoprostol ≥ 600 µg.

There was a statistically significant difference in the composite outcome ‘maternal death or severe morbidity’ for the comparison of misoprostol versus placebo (12 studies; average RR 1.70, 95% CI 1.02 to 2.81; Tau² = 0.00, I² = 0%) but not for the comparison of misoprostol versus other uterotonics (17 studies; average RR 1.50, 95% CI 0.50 to 4.52; Tau² = 1.81, I² = 69%). When we excluded hyperpyrexia from the composite outcome in exploratory analyses, there was no significant difference in either of these comparisons.

Pyrexia > 38°C was increased with misoprostol compared with controls (56 studies, 2776/25,647 (10.8%) versus 614/26,800 (2.3%); average RR 3.97, 95% CI 3.13 to 5.04; Tau² = 0.47, I² = 80%). The effect was greater for trials using misoprostol 600 µg or more (27 studies; 2197/17,864 (12.3%) versus 422/18,161 (2.3%); average RR 4.64; 95% CI 3.33 to 6.46; Tau² = 0.51, I² = 86%) than for those using misoprostol 400 µg or less (31 studies; 525/6751 (7.8%) versus 185/7668 (2.4%); average RR 3.07; 95% CI 2.25 to 4.18; Tau² = 0.29, I² = 58%).

Authors' conclusions
Misoprostol does not appear to increase or reduce severe morbidity (excluding hyperpyrexia) when used to prevent or treat PPH. Misoprostol did not increase or decrease maternal mortality. However, misoprostol is associated with an increased risk of pyrexia, particularly in dosages of 600 µg or more. Given that misoprostol is used prophylactically in very large numbers of healthy women, the greatest emphasis should be placed on limiting adverse effects. In this context, the findings of this review support the use of the lowest effective dose. As for any new medication being used on a large scale, continued vigilance for adverse effects is essential and there is a need for large randomised trials to further elucidate both the relative effectiveness and the risks of various dosages of misoprostol.

Postpartum misoprostol for preventing maternal mortality and morbidity

OBJECTIVE
To compare the postpartum uterotonic effect and side effects of misoprostol administered by different routes.


STUDY DESIGN
Fifty women were given misoprostol 400 microg either by the oral solution, oral tablet, rectal or vaginal route, or intramuscular syntometrine 1 ml after spontaneous vaginal delivery. Pre- and post-treatment uterine activity were measured with intrauterine pressure catheters.


RESULTS
Uterine activity produced by oral solution misoprostol 400 microg was significantly higher than that of oral tablet, rectal and vaginal misoprostol (P = 0.004, 0.002, respectively). Onset of action after oral solution misoprostol was faster than by the oral tablet (P = 0.01), rectal (P < 0.001) and vaginal (P< 0.001) routes. Shivering and pyrexia were most common with oral solution misoprostol. Maximum body temperature recorded was significantly higher with oral solution misoprostol than with oral tablet, rectal and vaginal misoprostol (P = 0.009, 0.001, respectively).


CONCLUSION
Different routes of administering misoprostol greatly influence the effects achieved. Oral solution misoprostol produces the fastest and strongest uterotonic effect, with the most side effects.

Does the route of administration of misoprostol make a difference? The uterotonic effect and side effects of misoprostol given by different routes after vaginal delivery. Review. European Journal of Obstetrics & Gynecology and Reproductive Biology 2004;113(2):191-198.

Retained placenta after vaginal delivery is diagnosed when a placenta does not spontaneously deliver within a designated amount of time, variably defined as a period of 18-60 mins. It may also be diagnosed if a patient experiences significant hemorrhage prior to delivery of the placenta. Normal placenta delivery requires adequate uterine contractions, with shearing of the placenta and decidua from the uterine wall and expulsion of the tissue. Thus, retained placenta can occur in the setting of significant uterine atony, abnormally adherent placenta, as with placenta accreta spectrum (PAS), or closure of the cervix prior to placental expulsion. Risk factors for retained placenta parallel those for uterine atony and PAS and include prolonged oxytocin use, high parity, preterm delivery, history of uterine surgery, and IVF conceptions. History of a prior retained placenta and congenital uterine anomalies also appear to be risk factors. Management entails manual removal of the placenta with adequate analgesia, as medical intervention alone has not been proven effective. Complications can include major hemorrhage, endometritis, or retained portions of placental tissue, the latter of which can lead to delayed hemorrhage or infection. Prophylactic antibiotics can be considered with manual placenta removal, though evidence regarding effectiveness is inconsistent. If hemorrhage is encountered, deployment of a massive transfusion protocol, uterine evacuation with suction, and use of intrauterine tamponade, as with an intrauterine balloon, should be initiated immediately. When a separation plane between the placenta and uterus is particularly difficult to create, PAS should be considered, and preparations should be made for hemorrhage and hysterectomy. Patients with risk factors for retained placenta should have a laboratory sample sent for blood type and antibody screening on admission to labor and delivery, and plans should be made for appropriate analgesia and preparations for hemorrhage if a retained placenta is encountered.

/pdf/retained-placenta-after-vaginal-delivery-risk-factors-and-1tvkawpjow.pdf

Retained placenta after vaginal delivery: risk factors and management

Journal de Gynecologie Obstetrique et Biologie de la Reproduction - Vol. 43 - N° 10 - p. 966-997

Prévention clinique et pharmacologique de l’hémorragie du post-partum lors de la troisième phase du travail

Objective

To test the effect of 800 μg of misoprostol orally on the prevention of manual removal of retained placenta.



Design

Multicenter, double-blinded, placebo-controlled, randomized trial.



Setting

One university and one non-university teaching hospital in the Netherlands.



Sample

99 women with retained placenta (longer than 60 min after childbirth) in the absence of postpartum hemorrhage.



Methods

Eligible women were administered either 800 μg of misoprostol or placebo orally.



Main outcome measures

Number of manual removals of retained placenta and amount of blood loss.



Results

Manual removal of retained placenta was performed in 50% of the women who received misoprostol and in 55% who received placebo (relative risk 0.91, 95% confidence interval 0.62–1.34). No difference in the amount of blood loss (970 vs. 1120 mL; p = 0.34) was observed between the two groups.



Conclusions

Administration of 800 μg of oral misoprostol, one hour after childbirth, does not seem to reduce the number of manual removals of retained placentas. The time elapsing results in the delivery of 50% of the retained placentas at the expense of an increased risk of postpartum hemorrhage.

No reduction of manual removal after misoprostol for retained placenta: a double-blind, randomized trial

Introduction: A description is given of the quality of life (QOL) of women who were treated with peripartum embolization or hysterectomy for major obstetric hemorrhage (MOH). Methods: Questionnaires assessing QOL, combined with questionnaires and drawings assessing illness perceptions, were used to compare women with MOH to reference groups provided by the questionnaires. Results: Women who experienced MOH have similar scores on QOL questionnaires compared to reference groups. Women treated with arterial embolization scored better than women treated with hysterectomy. Partners of women with MOH scored better on QOL questionnaires than reference groups. Drawings reflect the major emotional impact of MOH. Discussion: MOH does not seem to have a negative effect on QOL 6–8 years after the event, although drawings and verbalizations indicate major emotional impact. More extensive follow-up is advised for early recognition of the need for psychological help. Women after embolization seem to have better QOL compared to women after hysterectomy.

/pdf/major-obstetric-hemorrhage-a-follow-up-survey-on-quality-of-eie79j4m03.pdf

Giel van Stralen

Papers

No reduction of manual removal after misoprostol for retained placenta: a double-blind, randomized trial

Major obstetric hemorrhage: a follow-up survey on quality of life of women and their partners