Dr. Sharon SheehanResearch Fellow in Obstetrics

TCD & CWIUH

• Postpartum haemorrhage (PPH)• Misoprostol• Indications for PPH – prevention & treatment• Contraindications & precautions• Side effects• Summary• Future research• Key recommendations

• Single most important cause of maternal mortality worldwide

• 30% all direct maternal deaths

• 150,000 women die each year

• Complicates 18% all deliveries

• Remains a significant problem for developing and developed world

Primary:

Bleeding from the genital tract > 500mls within 24 hours of delivery

Secondary:

Bleeding from the genital tract between 24 hours and 6 weeks postpartum (recently expanded to 12 weeks)

Primary:

Bleeding from the genital tract > 500mls within 24 hours of delivery

Secondary:

Bleeding from the genital tract between 24 hours and 6 weeks postpartum

• 4 T’s

• Tone (70%)• Trauma (20%)• Tissue (10%)• Thrombus (<1%)

• 4 T’s

• Tone (70%)• Trauma (20%)• Tissue (10%)• Thrombus (<1%)

Prostaglandin E1 analogue

Registered since 1985 as “CYTOTEC” for the treatment of peptic ulcers

Effect on uterine contractions quickly noted

Despite this effect, not approved for use in obstetrics & gynaecology in most countries

Initially developed for oral use

Other routes of administation include:Vaginal, sublingual, rectal and buccal

Allows cervical smooth muscle relaxation

Increases intracellular calcium

Facilitates myometrial contraction

Prevention Treatment

Stable, orally active, cheap uterotonic

No need for needles & syringes

Would appear ideally suited to PPH prevention and highly attractive in developing world

Oxytocin is the current gold standard(↓ risk of PPH by > 50-60%)

Many studies have compared:

misoprostol v. placebo

misoprostol v. oxytocin

Hospital setting (Gulmezoglu, Lancet 2001)Compared to oxytocinLess effectiveMore side effects

Community setting (Derman, Lancet 2006)Placebo controlled trial↓ Risk of PPH

Cochrane Review (Gulmezoglu 2007) 37 trials

Misoprostol versus placebo8 trials400ug and 600ug600 ug – may be effective

Misoprostol versus oxytocin16 trialsHeterogenous Greater risk of PPH (RR 1.32, 95% CI 1.16-1.51)More side effects

Mean plasma concentrations of misoprostol over time

Mean plasma concentrations of misoprostol over time

Shortest time, highest peak, greatest bioavailability

Use when injectable conventional uterotonics are not available

Use when injectable conventional uterotonics are not available

600 ug orally or sublingually as a single dose

20 mins

20 mins

20 mins

Single blinded, assessment bias

Pilot study, insufficient power

Cochrane Review (Mousa 2006) 3 trials

Misoprostol versus placebo2 trials (398 women)600ug – 1000ugNo significant reduction in maternal mortalityMore side effects

Misoprostol versus oxytocin and syntometrine1 unblinded trialBetter response with rectal misoprostol

2 recent RCTs (hospital settings)

Misoprostol SL v. Oxytocin

Not exposed to oxytocin (Winikoff, Lancet 2010)Confirmed oxytocin is the drug of choiceRisk of additional blood loss ≥ 300mls – 78% more frequent with misoprostol

Exposed to oxytocin (Blum, Lancet 2010)Oxytocin is the drug of choiceRisk of additional blood loss ≥ 300mls – 12% more frequent (not significant) with misoprostolMore side effects

If conventional uterotonics are not availableAs a second-line agent

600 ug orally or sublingually as a single doseIf continued haemorrhage,• Repeat after 2 hours• Allow 6 hours lapse if side effects from initial dose

Intraumbilical use of misoprostol for retained placenta has been described with benefit

Further work needed though as RELEASE Study (Weeks, Lancet 2010) demonstrated no effect of intraumbilical oxytocin use

Allergy to misoprostol or other prostaglandins

Usual 3rd stage precautionsBreastfeeding – small amounts may appear, no known consequences

Generally safe and well tolerated

DiarrhoeaN & VFever & chillsHyperpyrexia

Huge variation in use, dose and route of administration highlights the need for a standard of care and clear guidelines

Successful management of uterine atony depends on staff being familiar with pharmacological agents available to them and that standard of care

Oxytocin is the gold standard

If conventional uterotonics are not available,

Misoprostol 600 ug orally or sublingually

For Prevention & Treatment of PPH

Consider as a 2nd line agent for PPH treatment, if conventional uterotonics fail

Future research needed

What about community settings?Future work needed

What if prophylactic misoprostol has already been used?

Extreme caution advised Side effects are dose dependentEfficacy is still unknown

Oxytocin is the gold standard

If conventional uterotonics are not available,

Misoprostol 600 ug orally or sublingually

For Prevention & Treatment of PPH

Consider as a 2nd line agent for PPH treatment

Future research needed

www. misoprostol. org

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Seeks to disseminate accurate information about misoprostol doses