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Evidence Based Use of Misoprostol in Second Trimester Induction
I was recently on call and we had 2 patients on our board having second trimester inductions, one for ruptured membranes at 17 weeks and another for fetal anomaly. Both patients were being treated with what seemed like a strange regimen of misoprostol, 400 mcg miso vaginally _and_ 400 mcg orally, every 4 hours. I had never heard of this regimen, and was wondering where it came from. None of the residents seemed to know, only that it had been passed down through some route to them.
It struck me as odd that people are using misoprostol in all kinds of different ways, despite the large amount of available evidence in the literature. In fact, it may be one of the most thoroughly studied topics in obstetrics, having been the subject of many randomized trials, a standard of research rarely achieved in our field. Studies have included both pharmacokinetic and clinical data. For better or for worse, abortion is the single most common procedure performed for women worldwide, and the patient population tends to be appreciative and willing to participate in research. Sadly, the mammoth amount of data available seems overlooked by the majority of practicing obstetricians, given the wide variation in practice I have observed. As such, I want to review a few of the major articles here.
Misoprostol for post partum hemmorhage? meh.
Ok – here’s a bit of rant inspired by something on call last night.
A multiparous patient labors for about 8 hours during a pitocin induction and develops a postpartum hemmorhage. Pit, methergine, and eventually hemabate are given with minimal response. The resident decides to place rectal misoprostol, and the uterus gains tone about a minute later. The resident remarks how well the miso worked and how we should us it more in the future.
This drives me crazy.
1) There are no venous channels that run from the rectum to the uterus. People act like they are doing something special by putting it in the rectum or even in the vagina, when in reality they are just using either as a mucous membrane to absorb the drug. The pharmacokinetics of miso are well studied, and it takes at least 1/2 hour to reach high levels of miso in the blood, and therefore in the uterus. There is no way that in one minute a lot of misoprostol got to the uterus. In fact, if one wanted the fastest effect, one should give it to the patient orally, as that causes the fastest rise in blood levels
2) Many studies have shown pitocin to be superior to misoprostol in treating and/or preventing postpartum hemmorhage. Why? Because of the above point – the IV pit gets to the uterus very fast. The miso takes 1/2 hour or more.
3) These thought open up a related irritation, which is the “novel” application of miso by placing it in the uterine cavity to cure uterine atony. The endometrium isn’t even a mucous membrane. Though the pharmacokinetics of this application have not been studied, I don’t think absorption will be so great, especially with all the blood rushing into the uterine cavity (the problem we’re trying to treat). Blood comes out of the uterus. It doesn’t go in.
So what happened in this case?
First the patient had atony. Then she got pit, which didn’t work well because pitocin receptors were very downregulated after the long induction. Then she got two effective uterotonics in fairly rapid succession – both of which were effective. Coincidentally, a bunch of misoprostol was placed rectally right around the time the IM methergine and hemabate reached the uterus, which despite its parental nature, still takes at least a few minutes. So residents, keep using that miso if you want, but I think its benefit is in preventing delayed atony 20 minutes later, not in the acute setting.
Of course, miso is great for third world nations where there are no IVs or refrigerators to keep parenteral uterotonics around. Or for causing first and second trimester abortions. Or for ripening the cervix in induction. Or for priming the cervix before a tough EMB. Or for dilating the cervix before a D and E procedure. Its just not that useful for postpartum hemmorhage, IMHO.
A related irritation – people who put patients on powerful antibiotics after they spike a 101.8 fever eight hours in at 400 mcg q6h second trimester miso induction, unruptured. What makes you think they are infected? They are unruptured, and happen to be on a powerful prostaglandin that reliably causes fever and chills at high doses. Please, just reassure the patient and give them some tylenol. Don’t use NSAIDs to break the fever, as the misoprostol is causing a fever downstream of the cyclooxygenase enzyme the the NSAID is blocking. Not that the NSAIDs will antagonize the miso (which somebody tried to convince me of once), just that they don’t work that well a miso inspired fever.
What do you think?
Nicholas Fogelson, MD
Academic OB/GYN.com
Academic OB/GYN 