What is the most effective uterotonic agent to prevent PPH?

Postpartum hemorrhage (PPH) is responsible for more than 25% of all maternal death around the world and is the leading cause of maternal mortality in low resource settings. It affects 5% of all women during labor and leads to substantial morbidity because of compromised maternal blood volume. 

Use of uterotonics during the third stage of labor could avoid a majority of complications due to PPH. WHO recently published updated guidance on uterotonics for the prevention of PPH, after which the Cochrane Review published the results of a network meta‐analysis to identify the most effective uterotonic agent.

The network meta‐analysis included 196 trials involving 135,559 women, with the majority of women having vaginal births (71.5%, 140/196) in a hospital setting (95.4%, 187/196). 

The WHO recommendations and results of the Cochrane analysis suggest:

To effectively prevent PPH, only one of the following uterotonics should be used: Oxytocin, Carbetocin, Misoprostol, Ergometrine/methylergometrine, Oxytocin, and ergometrine fixed-dose combination.

Oxytocin (10 IU, IM/IV) is the standard recommended drug of choice for prevention of PPH in all cases. The drug has minimum side effects and is cost effective too. The main problem with Oxytocin is it requires refrigeration and rapidly loses its potency if stored at room temperature.

The use of carbetocin (100 µg, IM/IV) is also recommended for the prevention of PPH for all births if cost is not the limiting factor. It is also not readily available everywhere.

Misoprostol, injectable prostaglandins, and ergometrine have no additional benefits compared with oxytocin. Misoprostol causes more undesirable effects than oxytocin (including nausea, vomiting, shivering, fever, and diarrhea).

Combination therapy involving ergometrine plus oxytocin combination (Syntometrine ®), misoprostol plus oxytocin combination and carbetocin have the additional desirable effects compared with oxytocin and can be used if oxytocin is unavailable. However, there is always a risk of undesirable side effects as compared to oxytocin. Injectable prostaglandins (carboprost or sulprostone) are not recommended for the prevention of PPH.

Misoprostol and oxytocin are not available in fixed-dose combination and require different routes of administration so its use in routine clinical settings may not be very feasible as compared to using them alone.

If using ergometrine (alone or in combination), it is important to rule out hypertensive disorders and cardiovascular diseases.

In low resource settings and non-availability of skilled healthcare personnel, misoprostol (400 µg or 600 µg) can be administered orally by the community or lay health workers.

WHO recommendations Uterotonics for the prevention of postpartum haemorrhage

Uterotonic agents for preventing postpartum haemorrhage: a network meta‐analysis

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Vaginal cleansing with antiseptic solution before cesarean section brings down postoperative infection: Cochrane review

A simple and inexpensive intervention of vaginal cleaning with the chlorhexidine-based or iodine-based solution immediately before cesarean section probably reduces the risk of endometritis after the procedure. The benefit could be more for women who underwent cesarean section while in labor or after rupture of membranes reports the results of a Cochrane review published 17 July 2018.

The current review is the fifth update on vaginal preparation before cesarean section and risk of subsequent infection by Cochrane; the first review was published in 2010 and subsequently updated in 2012, and twice in 2014.

Cesarean section is the most commonly performed operation in obstetrics, with 1 in 3 babies being born by cesarean section. Nearly 25% of women have endometritis and 10% of women develop skin infection after C-section.

Pre-op or intra-op antibiotic prophylaxis has not been able to bring down the rate considerably.

The Cochrane researchers searched the Cochrane Pregnancy and Childbirth’s Trials Register, the WHO International Clinical Trials Registry Platform (ICTRP) (10 July 2017), ClinicalTrials.gov, and reference lists of retrieved studies.

The review included 11 trials with a total of 3403 women in whom vaginal preparation was done immediately before the start of the cesarean section. Most of the trials used Povidone-iodine (n=8), while the rest used chlorhexidine (n=2) and benzalkonium chloride (n=1).

The control group included women with no vaginal antisepsis preparation (eight trials) or those in whom saline vaginal preparation (three trials) was used.

Vaginal preparation with the antiseptic solution immediately before cesarean delivery probably reduced the risk of endometritis by 64% (average risk ratio (RR) 0.36, 95% confidence interval (CI) 0.20 to 0.63).

It was not possible to separately analyze the risk reduction in a subgroup of women who were in labor or in women whose membranes had ruptured when antiseptics were used. 

Risk of postoperative fever or surgical wound complications may also be brought down by the use of vaginal antisepsis, but the confidence interval around the effects for both outcomes was very wide consistent with insufficient data.

Composite outcome of wound complication or endometritis was reduced by 54% in two trials consisting of 499 women (RR 0.46, 95% CI 0.26 to 0.82).

No adverse effects were reported with either the povidone-iodine or chlorhexidine vaginal cleansing.

The quality of evidence using GRADE was moderate for all reported outcomes. The authors downgraded the outcome for post-cesarean endometritis and composite of wound complications or endometritis because of bias in the involved study and broader CI.

The recommend that healthcare providers may continue using vaginal antisepsis preparation by either using povidone-iodine or chlorhexidine before performing a cesarean delivery.

Abstract

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