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The gentlebirth.org website is provided courtesy of
Ronnie Falcao, LM MS, a homebirth midwife in Mountain View, CA

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Pharmaceutical Induction - Pitocin and Cytotec (Misoprostol)

Why women shouldn't fear home birth
by Mayim Bialik, Ph.D.
This short essay is humorous, honest, insightful and inspiring.

See also:

Subsections on this page:



IMPORTANT - Postpartum use of Cytotec/misoprostol is very different from prenatal or intrapartum use, i.e. before the baby is born.  During labor, before the baby is born, Cytotec can cause contractions that are too strong for the baby . . . they can squeeze the placenta so tight for so long that there's not enough oxygen getting through to the baby; this can cause severe fetal distress.  Or, if the baby is not fitting into the pelvis (obstructed labor), the very strong contractions caused by Cytotec can actually cause a tear in the birthing woman's uterine muscle, which is called a uterine rupture.

After the baby is born, contractions caused by Cytotec given to the mother no longer affect the baby.  After the baby is born, the risk of uterine rupture also goes away because once the baby is outside the mother's body, there is no possibility of an obstructed labor.

I have heard from clients who are very concerned about my use of postpartum Cytotec for placenta problems or hemorrhage, even though it is more effective than pitocin or methergine in some cases. It's important for birth professionals to educate birthing women about the difference between pre-birth and post-birth use of Cytotec.

NOTE - Much of this material is from several years ago, mostly before 1998.  Since then, lots more research has been done, and some good summary articles have been written.
Please pay attention to the dates of the references articles!



Resources



Reducing Pitocin Use Reduces C-Sections!

Hospital’s Oxytocin Protocol Change Sharply Reduces Emergency C-Section Deliveries

By Betsy Bates, 6/19/09

"The modification of the oxytocin infusion protocol at a large university-affiliated community hospital nearly halved the number of emergency cesarean deliveries over a 3-year period, reported Dr. Gary Ventolini.
.  . .
“More and more data are showing us that we are using too much oxytocin too often,” Dr. Ventolini, professor and chair of obstetrics and gynecology at the university, said in an interview.



Study Finds Adverse Effects of Pitocin in Newborns [ACOG, 5/7/13] - "Induction and augmentation of labor with the hormone oxytocin may not be as safe for full-term newborns as previously believed . . . These results suggest that Pitocin use is associated with adverse effects on neonatal outcomes. It underscores the importance of using valid medical indications when Pitocin is used.”



Oxytocin Halt Not Tied to Cesarean Boost
-  By David Douglas [9/21/12] - "Once oxytocin has induced active labor, the drug can be stopped if regular contractions continue to generate cervical change, a new report says.

"Discontinuing the oxytocin under those circumstances doesn't increase the cesarean delivery rate, according to Pennsylvania-based researchers.

"But overall, women randomized to oxytocin discontinuation had longer labor, as Dr. Joanne N. Quiñones, senior author of the report, noted in email to Reuters Health. They also had a higher risk for chorioamnionitis related to intrauterine pressure catheter (IUPC) use and duration of membrane rupture."

This is great news for women in situations where induction is medically advised but who want to avoid unnecessary drugs.  Obviously, allowing the body to drive the rhythm of labor is going to take longer than adding additional oxytocin in the form of pitocin.  Risks associated with rupture of membranes and IUPC can be avoided by not rupturing membranes artificially and not using the IUPC.  The IUPC may be necessary when pitocin is used to augment active labor when there is a lack of progress without it.  But it shouldn't be necessary when pitocin is used just to get labor over the threshold into active labor.


Methods of Induction of Labour - A Systematic Review [Medscape, 12/22/2011]


UCSF/Stanford Team Finds Induction Need Not Increase C-Section Risk [8/18/09] - this seems to say that timely induction helps reduce c-sections (presumably getting the baby out before the head hardens), but the OBs need to be patient . . . not running the pit so high that it causes fetal distress, and waiting for the pitocin to work, i.e. PATIENCE!

When Research is Flawed: Can You Prevent Cesarean Sections by Inducing More Labors? by Henci Goer

Commentary on: Nicholson, J. M., Yeager, D. L., & Macones, G. (2007). A preventive approach to obstetric care in a rural hospital: Association between higher rates of preventive labor induction and lower rates of cesarean delivery. Ann Fam Med, 5(4), 310-319. [Abstract]


Amniotic-fluid embolism and medical induction of labour: a retrospective, population-based cohort study.
Kramer MS, Rouleau J, Baskett TF, Joseph KS; Maternal Health Study Group of the Canadian Perinatal Surveillance System.
Lancet. 2006 Oct 21;368(9545):1444-8.

INTERPRETATION: Medical induction of labour seems to increase the risk of amniotic-fluid embolism. Although the absolute excess risk is low, women and physicians should be aware of this risk when making decisions about elective labour induction.


Metabolic acidosis at birth and suboptimal care--illustration of the gap between knowledge and clinical practice.
Jonsson M, Nordén-Lindeberg S, Ostlund I, Hanson U.
BJOG. 2009 Oct;116(11):1453-60. Epub 2009 Jul 28.

CONCLUSION: Metabolic acidosis at birth is often associated with suboptimal intrapartum care. The high rate of suboptimal care with regard to oxytocin use and fetal surveillance illustrate a gap between guidelines and clinical practice. Metabolic acidosis and related neonatal morbidity could potentially be prevented in 40-50% of cases. The adherence to guidelines must be checked. [Ed: These conclusions are a little vague that many cases of suboptimal care were really hyperstimulation associated with pitocin.]

Response from a hospital-based midwife:

Although this is not news to many of us, it is always a good thing to review and remember the possible outcomes of the mismanagement of Pitocin and the importance of due diligence when it comes to abnormal tracings.  Our hospital has revamped their Pitocin Protocol and it is possibly in response to research like this. They are suggesting increasing the Pitocin dose up and stopping at 6 milliunits, whereas before we would go up to 24 and then the nurses ask for an order to go up to 30.

So this is a huge change based on research like this but also I suspect on research that states there is no need to go higher than 6 mus in order to create cervical change. The nurses can still increase the dose depending on the uterine activity but it does stop them pushing up the dose beyond what the uterus needs.

[Ed: Yes!  It makes sense to nudge the pitocin up just to the level where cervical change is occurring.  The original meaning of induction was to get the level of pitocin just up to the point where the woman's body would take over to keep labor going.  We need to go back to this model to reduce complications of hyperstimulation from pitocin overuse.]


Women Induced in Morning Require Fewer Interventions [Medscape is free.]

Morning compared with evening induction of labor: a nested randomized controlled trial.
Dodd JM, Crowther CA, Robinson JS.
Obstet Gynecol. 2006 Aug;108(2):350-60.


With routine induction on the rise, we are also seeing an increase of babies who are presumed to be mature enough to be born but are actually premature at birth and need intensive care to survive.

How can this happen with good dates from early ultrasound?  Simple. Not all babies have a standard 40-week gestation.  Some will appear "term" at 37 weeks, others not until 44 weeks.  This is normal biological variability similar to the different timetables for babies cutting their first teeth, taking their first steps, or speaking their first words.

Genetic heritage has a huge effect on a baby's natural gestation length.


Induction of labour - Excellent Patient Education from Kent Midwifery Practice in the UK (Kay Hardie and Virginia Howes)
This is a good critique of the classic multi-center study that is often used to justify induction, and which is now so old that it is inappropriate as a basis for such a serious intervention.


LEGAL ISSUES AND RISK MANAGEMENT: Best Practices in Perinatal Care: Evidence-Based Management of Oxytocin Induction and Augmentation of Labor
Laura R. Mahlmeister PhD, RN

Journal of Perinatal and Neonatal Nursing
October/December 2008
Volume 22 Number 4
Pages 259 - 263


The Seduction of Induction - excellent slideshow from Penny Simkin.


Four Parameters Predict C-Section Risk After Induction of Labor - British researchers have devised a model incorporating maternal body mass index, height, cervical length on transvaginal ultrasound and parity to predict the risk of cesarean section after induction of labor.


Induction Dangers, Compiled by Leilah McCracken for birthlove.com, a subscription site that is well worth the small cost!  [Ed: birthlove.com is not available at this time.]


Policy of Induction of Labor at 41 Weeks Associated with Excessive Use of Medical Interventions

When to induce labor for post-term? A study of induction at 41 weeks versus 42 weeks.
Fok WY, Chan LY, Tsui MH, Leung TN, Lau TK, Chung TK.
Eur J Obstet Gynecol Reprod Biol. 2006 Apr 1;125(2):206-10. Epub 2005 Aug 31.

CONCLUSION: Compared to routine induction at 42 weeks, induction at 41 weeks is associated with a significantly higher risk of use of medical interventions and associated complications, with no observable benefits.

The following information is from Volume 3, Issue 3 of Research Summaries for Normal Birth, July 2006, from the Lamaze Institute for Normal Birth:

Summary: This retrospective study compared outcomes of “post-term” pregnancies occurring when a hospital protocol required induction at 42 weeks with those occurring after the protocol was changed to require routine induction at 41 weeks. Prior to the protocol change, a routine cardiotocogram (non-stress test) was performed at 41 weeks and if normal, induction was scheduled at 42 weeks. The hospital was a university-affiliated obstetric unit in Hong Kong performing over 5000 births per year.

Routine induction of labor at 41 weeks only reduced the mean gestational age at delivery by 3 days while more than doubling the rate of labor induction in women at or beyond 41 weeks of gestation. The average length of labor was significantly longer, and use of epidural analgesia was significantly more common among “post-term” women after the protocol changed. There were no differences in maternal characteristics, mode of birth, or newborn outcomes across the two groups. Outcomes were unchanged when the researchers repeated their analyses controlling for parity.

Significance for Normal Birth: Complex hormonal signals between baby and mother allow labor to begin on its own. While this may happen for many women up to two weeks (or more) after the estimated due date, many care providers believe that routine induction at 41 weeks is associated with improved perinatal outcomes. This assertion is based on previous research that may be critically flawed.

This retrospective study is not big enough to detect differences in rare adverse maternal and infant outcomes, but it provides compelling data that suggest that inducing labor at 41 weeks is associated with very high rates of obstetric interventions. Use of pharmacologic induction agents and epidural analgesia became much more common on this obstetric unit once the clinical protocol began requiring induction of labor at 41 weeks. Labor was also considerably longer when induction was required at 41 weeks, compared with labors occurring at the same hospital prior to the protocol change. The trade-off of such excessive intervention was a mere 3-day difference in the average gestational age at birth. Women facing induction at 41 weeks need to know that waiting just a few more days will likely allow labor to start on its own and help avoid potentially harmful interventions.


Routine induction of labour at 41 weeks gestation: nonsensus consensus. [Full text] [Ed: birthlove.com is not available at this time.]
Menticoglou SM, Hall PF.
BJOG. 2002 May;109(5):485-91.


Evaluation of glyceryl trinitrate, misoprostol, and prostaglandin E2 gel for preinduction cervical ripening in term pregnancy
Yuthika Sharma, Sunesh Kumar, Sunita Mittal, Renu Misra and Vatsla Dadhwal
Journal of Obstetrics and Gynaecology Research
Volume 31 Issue 3 Page 210  - June 2005

Conclusion: The findings of the present study suggest that GTN is safer, but less efficacious, compared with prostaglandins for preinduction cervical ripening at term.  [Ed. Perhaps repeated applications of the safer GTN would ultimately be as effective as a single use of prostaglandins?]


 
Induction By Request from the March of Dimes.


 Cesarean delivery after elective induction in nulliparous women: The physician effect.
 Luthy DA, Malmgren JA, Zingheim RW.
Am J Obstet Gynecol. 2004 Nov;191(5):1511-5.

Conclusion Nulliparous women [i.e. women having a first baby] are at a significant increased risk of cesarean delivery if elective induction is performed. The individual physician has a contributing effect to this increased risk.


Labor induction with dinoprostone or oxytocine and postpartum disseminated intravascular coagulation: a hospital-based case-control study.
De Abajo FJ, Meseguer CM, Antinolo G, Garcia Rodriguez LA, Montero D, Castillo JR, Torello J.
Am J Obstet Gynecol. 2004 Nov;191(5):1637-43.

CONCLUSION: The pharmacologic induction of labor is associated with an increased risk of postpartum DIC, regardless the substance used. Although the absolute risk seems to be quite low, the obstetricians should not neglect it, in particular for the special risk groups identified [a maternal age older than 34 years (AOR = 9.5; 95% CI: 2.4-37.7), complications during pregnancy (AOR = 5.5; 95% CI: 1.3-22.8), and a gestational age of over 40 weeks (AOR = 3.5; 95% CI: 1.1-11.1)]



Induction Statistics



Births by Day of the Year - a panel chart below showing data for the period from 1 November of one year through 31 January of the following year.



Doula Perspectives About Inductions Leading to Cesareans



I am about to pull my hair out here with what seems to be an INDUCTION EPIDEMIC.

In the past year I have had eight doula clients; six were induced. If my memory serves me correctly, only one of these inductions was truly needed. Most of my clients are middle-class women who "want to go natural and avoid an epidural but will get one if they really can't handle it." They know enough to want to hire a doula, but aren't really "earth mommas" Here's how things went:

  1. induced at 41.5 weeks, 0-2 Bishop's score; agreed to do it because mother was in from out of state; ended in csection.
  2. induced at 40 weeks, twice.  She begged the doctor to induce her because she was sick of being pregnant.
  3. induced at 41.5 weeks; don't recall why.  Fast labor.  Ended well.
  4. induced at 40.5 weeks, low amniotic fluid.  Ended well.
  5. induced at 39 weeks; IVF pregnancy; due Christmas day, doctor going out of town 12/26-31; ended in csection.
  6. induced at 41.5 weeks, 0-2 Bishop's score; agreed because parents here from China and leaving in 2 days, ended in csection.
To say I am discouraged is putting it mildly.  I give them the information on other ways to get labor started (ala Penny & Ina May's books, etc.) and the risks of induction.

There seems to be an induction epidemic here too! I tell all of my clients about Bishop scores and ask them to ask their doctor what their Bishop score is when they bring up induction. Then I direct them to the online Bishop score tool at childbirth.org where they can read for themselves their likelihood of having a successful, non-interventive birth. I also give them the article "Let the Baby Decide" and some info on natural induction methods to try getting their cervix ready IF there is a medical indication for induction-which is rare.


What make me SO MAD is when docs induce and even I know it isn't  going to work and you can see hours and hours of work and pain from the crazy ctx and they just keep letting it go as if it is normal.

I seriously am ready to tell clients that if their Bishop's score is unfavorable and they are not willing to wait, they just need to save themselves the trouble and schedule a c-section!!!!


I started taking  a tough-love approach and I say over and over again:

You have been pregnant for 280 days so far, give or take. Labor and Delivery is the natural conclusion to this state and it is up to you and your baby to finish the job when your body and baby tell you to.  This body and baby know on a cellular level how to birth and be born--they are tied up in an intricate dance of the most graceful kind.  Do you really want to interrupt what has been working so well for all of these months?

I know you're tired, I know you feel like an elephant, I know you are ready to look like a mom who has a baby in her arms.  But what you are doing now is the ultimate act of motherhood--you are honoring your child's needs by letting her do this at her developmental level.  Although we say a child should be reading and writing comfortably by the winter of 1st grade there is no parent or teacher who throws a child into a specialist the day the calendar says 'first day of winter'.  We look at process and change.   Has your baby been growing?  Do you feel how that baby is becoming ready for this world?  That is progress and change--all remarkably just as it should be.

Today it is the 9th of March and you are 40 weeks and 2 days pregnant.  I can guarantee you that when you see April on your calendar you will have a baby in your arms and if you wait for that baby to give you her signal that she is ready for that time, you will be looking back at a labor that is very different from the one that is highly typical of inductions and rarely with exception.

Then I talk about 3 or 4 different induction stories and tell them again to finish the job and honor their body and their baby.

If they are getting flak from their docs I tell them to tell the doctor that they feel fine, baby feels fine, they are fine with NSTs as the doc wants.

What make me SO MAD is when docs induce and even I know it isn't going to work and you can see hours and hours of work and pain from the crazy ctx and they just keep letting it go as if it is normal.  It is the only situation you will me tell clients that they need to ask for vaginal checks because they get that hyperstim of the uterus which measures like a ctx although even on the EFM does not look like one, and if you feel the belly, it doesn't feel like one--it feels like a muscle in a panic!  And it rarely produces change.

I am sick of the suffering the women go through just to save a couple days! I put this up on my website:
http:



Philosophy of Induction



This is a fabulous article from Mothering Magazine:

Let the Baby Decide: The Case against Inducing Labor
Issue 105, March/April 2001
By Nancy Griffin


In this 7/12/06 Wall Street Journal article, THE INFORMED PATIENT - New Practices Reduce Childbirth Risks Amid Soaring Liability Costs, Hospitals Curb Use of Drugs And Other Procedures to Speed Labor By LAURA LANDRO, she writes, "Inappropriate use of labor-inducing drugs" is one of "The top six contributors to obstetrics litigation".

"Pitocin is used like candy in the OB world, and that's one of the reasons for medical and legal risk," says Carla Provost, assistant vice president at Baystate, who notes that in many hospitals it is common practice to "pit to distress" -- or use the maximum dose of Pitocin to stimulate contractions.



Pit To Distress



"Pit to Distress": Your Ticket to an "Emergency" Cesarean?

"Pit to Distress" 2: Why We Are All Distressed



Connection between Pitocin Induction and Autism



Dr. Lewis Mehl-Madrona is the only person I've heard offer an explanation for the presumed mechanism for the pitocin/epidural/autism connection

The above is out of date, as of Aug., 2013.  Dr. Mehl-Madrona was just eleven years ahead of his time.



Induced Labor Linked to Raised Risk of Autism, Study Suggests - Male children seem to be most vulnerable, researchers report [8/12/13 from webmd.com]



Association of Autism With Induced or Augmented Childbirth in North Carolina Birth Record (1990-1998) and Education Research (1997-2007) Databases.

Gregory SG, Anthopolos R, Osgood CE, Grotegut CA, Miranda ML.
JAMA Pediatr. 2013 Aug 12. doi: 10.1001/jamapediatrics.2013.2904. [Epub ahead of print]

CONCLUSIONS AND RELEVANCE Our work suggests that induction/augmentation during childbirth is associated with increased odds of autism diagnosis in childhood. While these results are interesting, further investigation is needed to differentiate among potential explanations of the association including underlying pregnancy conditions requiring the eventual need to induce/augment, the events of labor and delivery associated with induction/augmentation, and the specific treatments and dosing used to induce/augment labor (eg, exogenous oxytocin and prostaglandins).



Editor's Note - Perhaps these studies are pointing the way to one path to autism prevention.  As a homebirth midwife, we cannot use pitocin to induce labor.  Our clients can take herbs or other alternative paths to trying to start labor, but we need the uterus to have lots of oxytocin receptors.  In order to increase oxytocin receptors, we encourage clients to take cottonroot bark tincture in the last weeks of pregnancy.; this herb is slightly estrogenic, which is what increases oxytocin receptors.

Since the association between autism and induction is stronger in boys, and boys tend to come a little later than girls, we can hypothesize that oxytocin receptors in the boy babies' brains are a little less mature at the time of induction.  In nature, labor cannot start until oxytocin receptors in the mother have increased to the level where they are responsive enough to oxytocin to initiate active labor; this would presumably have a high level of correlation with the development of oxytocin receptors in the baby's brain.  Perhaps this process is fragile to the disruption of early birth through induction.  (Note that "augmentation" is often really "induction" because labor wasn't really established.)

It would be interesting to note whether babies born early by non-labor cesarean also are more prone to autism; this would point to an incomplete development of oxytocin receptors in the baby's brain.  If that's the case, then autism might be prevented by encouraging pregnant women facing induction to take cottonroot bark or other estrogenic compounds to increase the oxytocin receptors in baby's brain before the birth.


Autism linked to induced or augmented labor, study says [8/12/13] - Male infants born in deliveries in which labor was both induced and augmented were 35% more likely to have autism than those whose mother did not have either of these treatments. For induction alone, risk was elevated 18%. For augmentation alone, risk went up 15%.



Low-Dose Pitocin



Low-Dose Pitocin



About Misoprostol (also known as Cytotec)



The FDA's PDR-style page about Cytotec


The Tatia Oden French Memorial Foundation - dedicated to the memory of the mother and baby who died as a result of inappropriate use of cytotec for induction.


This is a fabulous article from Mothering Magazine:

Induced and Seduced: The Dangers of Cytotec
Issue 107, July/August 2001
By Ina May Gaskin

The Misoprostol/Cytotec Controversy from Ina May Gaskin's site


Induction of Labor: The Misoprostol Controversy (Full-Text Article)
Is misoprostol safe and effective for inducing labor in carefully selected women? from Journal of Midwifery & Women's Health, Jul 2003 Alisa B. Goldberg, MD, MPH, Deborah A. Wing, MD


4/02 -  The FDA said yesterday that it has changed the label of the drug Cytotec to reflect the fact that it is widely used by doctors to induce labor and is also part of the FDA-approved regimen for inducing medical abortion, Reuters Health reports.  The label for Cytotec, which is known generically as misoprostol and was originally approved to treat ulcers, had stated that pregnant women should not take the drug under any circumstances, a warning that the FDA has now removed.  The change reflects the frequent off-label use of the drug by obstetricians and gynecologists to induce labor and delivery.  In addition, Cytotec, which is made by Pharmacia, is prescribed in combination with the drug mifepristone (RU-486) to induce abortions early in pregnancy.  The new label will keep the warning that women who are taking Cytotec to treat ulcers should not become pregnant (Reuters Health, 4/18).  An FDA summary of the label changes is available online.  In addition, the new label itself may be viewed online.


ACOG Supports Use of Misoprostol for Medical Abortion and Labor Induction - (November 30, 2000)


The Devil Cytotec - An excellent collection of relevant information and links.    [As of spring, 2002, the BirthLove site is by subscription only - it's well worth the $10 membership fee.]


Cytotec is the trade name of a synthetic prostaglandin analogue, misoprostol. It is marketed in the USA as a specific drug for the prevention and treatment of NSAID induced stomach ulcers. In Brazil it is widely used as an abortifacient. There have been several clinical trials of its use as a cervical ripening and labor inducing agent. It is extremely effective at very low doses, is very cheap, and has been used on many many women without their being aware that it really is still an experimental use. A good MedLine search will get you gobs of references...if you don't have access to MedLine through the hospital, go to medscape (www.medscape.com) or a similar site. Keywords "misoprostol" and "pregnancy". The green journal (Obstetrics and Gynecology) has at least one article on misoprostol in almost every issue the last year! I just picked one at random off my shelf...Vol 88#4, October 1996...it has an article detailing an RCT of vaginal misoprostol for the induction of labor.


Misoprostol. A synthetic prostaglandin, it is approved by the FDA for the prevention of nonsteroidal anti-inflammatory, drug-induced gastric ulcers. It also induces uterine contractions and expulsion of uterine contents and thus can be used in combination with mifepristone or methotrexate. When taken orally, it is rapidly absorbed and undergoes de-esterification to its active free-acid compound. It reaches peak serum levels 15 to 30 minutes after oral administration and has a terminal half-life of 20 to 40 minutes. The usual dose for the prevention of gastric ulcer is 200mcg po qid. Misoprostol is used as an abortifacient in combination with methotrexate or mifepristone.

For use as an abortifacient in Europe, misoprostol 400mcg is taken orally 36 to 48 hours after mifepristone. When oral versus intravaginal misoprostol was studied with methotrexate, 800mcg of misoprostol intravaginally was more effective and had fewer side effects than 400mcg of oral misoprostol.[8] Misoprostol 800mcg has also been studied intravaginally in combination with mifepristone.[9-11] With methotrexate, however, the slight increased effectiveness of a misoprostol suppository does not warrant the added costs of compounding one.[12] After methotrexate, therefore, the recommendation is to use misoprostol tablets administered by finger into the vagina.


Misoprostol is commonly used to soothe stomach irritation. It is effective at inducing labor, half a tablet in the vagina every 4 hrs prompted 88 percent (15 of 17) pregnant women to give birth within 36 hrs. (With standard therapy, 47% went that quickly.)

THIS STUDY IS TOO SMALL TO DRAW CONCLUSIONS FROM 

I must say that I have heard some great things about cytotec myself. I know some people who have used it, and say that they have pretty good luck with it. It sounds like your ladies are pretty classical of its effects. 2 hour labors and such. Just be careful. I would have to say that the biggest danger is leaving the woman alone. The stuff turns the cervix to complete MUSHIE and opens it with a couple of contractions. So whatever you do, remember that you must not stay gone too long. You are pretty much committed to it after that first dose.

I was reading a study recently on why Cytotec is so effective. It turns out that the type of prostaglandin that was previously thought to be the best/closest precursor to labor/oxytocin is a type E prostaglandin. (we are talking about the "gel" here.) Cytotec is a type F prostaglandin, and is obviously showing much better results with its use in terms of a prostaglandin to induce labor.



Cytotec References/Abstracts




Misoprostol vaginal insert for successful labor induction: a randomized controlled trial.
Obstet Gynecol.  2011; 117(3):533-41 (ISSN: 1873-233X)


Oral misoprostol or vaginal dinoprostone for labor induction: a randomized controlled trial. [Medscape summary - Medscape registration is free]
Dallenbach P, Boulvain M, Viardot C, Irion O.
Am J Obstet Gynecol 2003 Jan;188(1):162-7

"CONCLUSION: We found no difference in terms of effectiveness and safety between low-dose oral misoprostol and vaginal dinoprostone used for induction of labor. This regimen avoids the excessive uterine contractility noted in previous studies, where higher doses of misoprostol were administered at longer intervals." [low-dose misoprostol was defined as 20 mcg given every 2 hours]


Oral Misoprostol Equivalent to Catheter Plus Dinoprostone For Labor Induction [Medscape registration is free]

Cervical ripening and induction of labor with misoprostol, dinoprostone gel, and a Foley catheter: a randomized trial of 3 techniques.
Barrilleaux PS, Bofill JA, Terrone DA, Magann EF, May WL, Morrison JC.
Am J Obstet Gynecol 2002 Jun;186(6):1124-9


Titrated oral misoprostol solution for induction of labour: a multi-centre, randomised trial.
Hofmeyr GJ, Alfirevic Z, Matonhodze B, Brocklehurst P, Campbell E, Nikodem VC.
BJOG 2001 Sep;108(9):952-9

New Approach to Misoprostol Delivery Reduces Risk of Uterine Hyperstimulation

WESTPORT, CT (Reuters Health) Oct 09 - Titrated administration reduces the risk that oral misoprostol will cause uterine hyperstimulation in pregnant women undergoing induction of labor.

Dr. G. J. Hofmeyr, of the University of Witwatersrand, South Africa, and colleagues conducted a randomized clinical trial comparing the effects of titrated oral misoprostol solution and vaginal dinoprostone. At hospitals in South Africa and Liverpool, UK, 695 women undergoing labor induction after 34 weeks of pregnancy were randomized to receive oral misoprostol solution or two doses of vaginal dinoprostone (2 mg) given 6 hours apart.

"The smallest preparation of misoprostol available in trial countries was a 200 µg tablet," the team explains in the September issue of the British Journal of Obstetrics and Gynecology. "For induction of labour a starting dose of 20 µg was required. To overcome the problem...we dissolved the tablet in 200 mL water."

After two or three doses, depending on the site, the dose was increased to 40 µg. The solution was administered every 2 hours until adequate contractions occurred.

The investigators observed no significant difference between the groups in failure to deliver vaginally within 24 hours. Sixteen percent and 20% of misoprostol patients and dinoprostone patients, respectively, required cesarean section (relative risk 0.80). Four percent of misoprostol patients and 3% of dinoprostone patients experienced hyperstimulation with fetal heart rate changes (RR 1.32).

Women with intact membranes and unfavorable cervices who were treated with misoprostol had a slower response to induction of labor than those treated with dinoprostone. The response was slower in patients treated with dinoprostone when membranes were ruptured. The team observed no significant differences in neonatal outcomes between the groups.

"A possible solution to the problem of hyperstimulation [with misoprostol]," Dr. Hofmeyr and colleagues suggest, "is the use of a single, small vaginal dose to achieve the local effect in women with unfavourable cervices, followed by frequent, small titrated oral doses to 'fine-tune' the uterine response." [Br J Obstet Gynecol 2001;108:952-959.]


Use of Misoprostol for Cervical Ripening [Medscape registration is free]



For Cervical Ripening



[from ob-gyn-l]


Is anyone using CYTOTEC for cervical ripening?? I understand that it has few side effects and only costs about forty cents per tablet. I would like any info you may have.


At my suggestion our high risk OB referral hospital tried cytotec - 1/2 tab per vagina - and after two cases of hyperstimulation stopped its use.


Did your colleague use half of a 100 microgram tablet or half of a 200 microgram tablet? It makes a huge difference. I have found that it works wonderfully, and the best response seems to be using 50 micro grams. There are a few pts who are very sensitive and take off with just a 25 ug dose.


2 tablets in one time few hours before a (D) & C. You don't need any D any more. But it is not approved for induction at term with living baby.


We use 50 micrograms of misoprostol in the posterior fornix every 4 hours until the cervix is "ripe" or until regular contractions (greater than 6-8 per hour) occur. A recent report in Obstetrics and Gynecology (Kramer et al., 1997; 89(3):387-391) reported on 100 micrograms in a similar regimen compared to IV oxytocin, with a significantly decreased time to delivery (585 versus 885 minutes). They reported that 70% of misoprostol patients developed tachysystole. We only rarely see this at the 50 microgram dosage. Wing et al. (AJOG 1995;172:1804-1810) reported tachysystole in about 37% of patients receiving 50 micrograms, but, again, we have not seen many problems with this. However, we provide continuous fetal monitoring in all our patients receiving misoprostol. The bottom line is the stuff works very well for cervical ripening, and many patients do not need oxytocin.

Finally, I had a patient recently with an 18 week fetal death in utero who rapidly progressed through labor and delivered the fetus, but did not deliver the placenta. Oxytocin and time did not help. I gave her 600 micrograms of misoprostol and she delivered the placenta 30 minutes later. There were no side-effects in this "series of one".


While we do not use it for ripening, we are using it (almost exclusively) for induction of labor in any patient whose cervix is <2-3 cm. We've done a local RCT comparing 50 mcg to 25 mcg and 50 is the superior dosage. We've seen no cases of hyperstimulation that did not respond to a 2 gram bolus of MgSo4. You can almost count on a delivery 12 hours after inserting the Cytotec tablet.

The usual side effects of prostaglandin are minimized with this medication...almost non-existent, though one must certainly exercise judgment with asthmatics.


We using cytotec 25-50 mcg for cervical ripening as well as for labor induction/augmentation. The common dose is 50 mcg. 25 mcg is used for patients with some uterine activity. Hyperstimulation, rarely occurs and is well controlled with terbutaline . No tachycardia observed. Delivery occurs after 2-3 doses.

It was used for labor induction for a patient with IUFD at 18 weeks. It worked fast, without the side effects of prostaglandins.

It was used successfully on patients who refused IV fluids.


Used Misoprostol for the first time this weekend (first time for me and for the hospital.) Started with Cervidil for twelve hours, then pit then cervidil then pit. No cervical change. The pharmacy cut a 200mg tablet into four (no 100mg tabs) and the first 'chunk' did nothing. The second piece had a rapid response and she delivered (from 80% / 2cm / posterior /firm /-2 station) to delivery) three hours into the second dose. She did have a large (1000cc) postpartum atonic bleed, which responded to bimanual massage and methergine. Do you see atony often, or was it just the induction meds, which occurs often in these situations?


Our hospital sponsored a dosage study comparing 50 mcg and 25 mcg for efficacy as well as complications. There was no increase in the incidence of postpartum hemorrhage due to atony. (N=150)


As you correctly surmised the placement of a tablet whether 50,100, or 200ug of misoprostol will remain for far more than 2-3hrs. The relevant data I have not seen published would be the absorption characteristics and measured serum levels of drug in the patient. It is likely that you will find a substantial spread as happens with many drugs absorption and bioavailability coefficients. A good example is the use of procardia for preterm labor. There are rapid and slow metabolizers of the drug. The only pregnancy study from Stanford showed markedly discrepant values which would then characterize the two populations. The March Obstet Gynecol 89: 392-397 (1997)has two articles on misoprostol for induction. The oral 100ug dose had an high rate of hyperstimulation. From my own experience with both terminations and induction, be very careful about the use of 100 or 200ug doses of drug.



Cytotec Induction at Term - Protocols



Protocol: Misoprostol (Cytotec) for Cervical Ripening and Induction of Labor
By Myer S. Bornstein, M.D. and Don Shuwarger, M.D., F.A.C.O.G.


Cytotec is a relatively new agent for cervical ripening/induction. There is no one protocol. However, the dosages most often used are 25 or 50 micrograms q 4 hours if contractions are less than q 3 minutes. The tablets are 100 micrograms and our pharmacy chops them up.


Our protocol is 50 mg every 4 hours to a max of 200 mg in one 24 hour period (never seen a woman who needed more than 100 mg total tho...). If it is a IUFD we use 100 mg at a dose. I was unfortunate enough to see a woman (viable baby) who received 200mg in 1 hour (PROM-FTA) she was a thick, posterior, high and tight but went to delivered in less than 3 hours... thank G-d the baby was OK despite the ctx. Again, as with the Laminaria, please research and develop a protocol before using a modality...and while you are at it develop an informed consent.


We are using it at Yale for cervical ripening, and although there is a format for how to give it, there is still controversy on to whom to give it. The protocol is for cervical ripening/induction. Pharmacy uses one of their nifty little pill cutters and sends us 1/4 of a 100microgram tablet (remember this stuff was made for treatment of ulcers!) Some places use more than 25 mcg.

The tablet is placed in the posterior fornix, and can be used with ROM. Mom is continuously monitored for a couple hours, and if she is not contracting regularly, she may go home. The dose can be repeated q4h as long as contractions are not more than every 3 minutes. The protocol says it can be given up to 5 cm. This is all very arbitrary, however, and I don't think there are any studies to say if this is the optimum use.

In our limited experience, most women go into active labor with just 1 or 2 doses. I think it is much better than PG gel for ripening, and works a lot better than pit if the cervix is not ripe.

However, I think it needs to be used with caution....at least til there is a greater experience with it. I have seen hyperstimulation with it, and it seems a lot like the buccal pit of yore in that if you have problems, you can't shut it off. Our practice has arbitrarily decided not to use it with oligohydramnios, IUGR or other situations where we feel that the fetus is entering labor in a compromised (or potentially compromised) state.


I have used Cytotec, but only in the hospital. 1/2 hr of monitoring is done prior to insertion to assure fetal well being ( a non-stress test essentially), and then 30 -60 minutes of monitoring after insertion to assess for contraction pattern and fetal response....

The standard dose on a woman with intact membranes is 50mcg every 4-6 hrs. Some practitioners use 25mcg every 4-6 hrs. I used 25mcg on women with SROM every 6, but some use the 50 mcg dose for that as well. You can administer the meds either vaginally or by mouth...different thoughts on each route. Theoretically, you can "wash out" the meds from the vagina in the event of fetal distress or uterine tachysystole (hyperstim)-- but I personally doubt that it works. I think it just makes the providers feel better!

My thoughts on the monitoring: You can do an Auscultated Acceleration test using a fetoscope or a Doppler and document those numbers prior to insertion. After insertion, you could do the same - (maybe at 15 min intervals for one hour) and additionally document the woman's contraction pattern and her response to them for that same time period.

I am not sure if I would feel comfortable with using it at home, though I might consider it. It seems that many of the women who receive it are pretty "quiet" for a few hours, but once the meds kick in- labor starts with a bang and keeps on going- sometimes with an uncharacteristic ferocity that scares me. The reason many people like the cytotec is that it can stimulate a labor faster than Pitocin and PG gel in many cases- but sometimes I wonder if the "faster" part is worth it. Contractions really do seem to come back to back, leaving little time for coping....(with the 50 mcg doses esp.) The smaller doses of 25mcg seem to be much more humane

It is a powerful little tablet that can work wonders and saves time, energy and money for many involved- but I think it should be used with caution and respect!


[from ob-gyn-l]

We've talked about Cytotec every few months or so on this list, so will just try to summarize. It's a prostaglandin developed in an oral form specifically to protect the stomachs of people who have a chronic need for NSAID use (arthritis, etc). Someone discovered that the oral pills can be used vaginally and have an effect similar to prostin gels, but MUCH more cheaply and without the need for hospitalization (if used carefully and judiciously). Some hospitals have been using Cytotec for inductions and have written protocols, but they seem scattered about - there sure aren't any around here. I've personally used it twice and had excellent results in women wanting homebirths, but going postdates. I'm sending my own protocol (below) for anyone interested. Again, I warn that I am no expert and I consider this protocol to be a "work in progress" - it will certainly change as I gather experience and information about this drug.


Cytotec Guidelines

A. Cytotec is not currently approved by the FDA for cervical ripening or labor induction. Client should be given complete informed consent.

B. Clinical indication must exist to justify the use of Cytotec for cervical ripening or labor induction and well-documented in the chart.

  1. Postdatism by good criteria
  2. Pregnancy at least at term by good criteria if concern re: macrosomia or need to prevent postdatism
  3. Documented blighted ovum/missed ab by sono and lack of natural miscarriage
C. Start with an intravaginal dose of no more than 50 mcg until client's individual sensitivity to Cytotec can be determined.

D. Use of Cytotec should always be preceded by careful prenatal exam to document fetal position, size, and well-being, as well as Bishop score of the cervix.

E. For ripening the cervix: Client may insert 50 mcg Cytotec (1/4 of a 200 mcg tablet) as far back into her vagina as she can reach (posterior fornix, if possible) at bedtime for several days as needed until desired change has occurred.

F. For labor induction: Start with ripening instructions as above; if labor does not ensue and there is no evidence of hyperstimulation of the uterus, client may increase dose to 100 mcg (1/2 of a 200 mcg tablet), repeating dose every 4-6 hours for up to 4 doses (?) in the absence of hyperstimulation until contractions are regular and cervical change is accomplished.

G. To induce miscarriage in cases of documented missed ab: Client may insert 100 mcg (1/2 of a 200 mcg tablet) as above; repeat dose in 4-6 hours x 1; should be watched carefully to make sure that miscarriage is complete and bleeding resolves appropriately as some clients may have incomplete miscarriage as a result of Cytotec.

H. Do not repeat Cytotec dose if adverse side effects or prolonged contractions result.


I just started looking this up. See Mundle, et al., "Vaginal Misoprostol for Induction of Labor," Ob Gyn 1996; 88:521-5. Patients who met reasonable criteria had a 50 microgram tablet (half of the standard 100 mcg. dose) placed in the fornix q 4 hrs. until labor occurred. They were compared to a Prostin group and there were no significant differences (e.g. C/S rate, hyperstim rate, low apgars, etc.)

Other protocols referred to are 25 mcg. q 2hrs., 50 mcg. q 3 hrs., or 100 mcg. given once, but these were not addressed in this paper.

What I would like to see is a study where we place a single misoprostol in the fornix in the office at 4:00 p.m., monitor, then send home, and begin the induction the next morning.


Misoprostol (Cytotec) is a synthetic PGE1 analogue.

For cervical ripening and induction:

  1. Do NST
  2. Insert 25 mcg. tablet in vagina
  3. Standard V.S.
  4. If patient with prior C/S insert IV and do T&S
  5. can repeat dose every four hours up to a total of 6 doses.
  6. Pitocin can be started four hours after last dose
  7. After three to four hours patient can ambulate.
  8. Watch for tachysystole, if occurs remove vaginal tablet (our cases have not shown any fetal distress)
Second Protocol Oral Dosing
  1. Do NST
  2. Give 100 mcg. tablet p.o.
  3. Standard V.S.
  4. If patient with prior C/S insert IV and do T&S
  5. Pitocin can be started four hours after last dose
After three to four hours patient can be discharged home and to return if labor ensues of the next day for induction. 

Two references on the cytotec induction I think you would be well to read and have handy: NEJM 333:537 (August 31, 1995.) This is the original article by Dick Hauskenecht. The second reference is from the Medical Letter 38:39. (April 26,1996). The reason I think it important that you have it, is that the anti-abortion legal group (out of Texas) just sent circulars out this week asking that complications from this method be reported to them. Thorough documentation of management would seem imperative.


Now we're using Misoprostol for induction. In 50 cases, we've only failed to get someone into labor once and our C/S rate is around 18%.


We use 25 micrograms vaginally q 2-3 hours until either labor starts, or the cervix is ripe, at which time we start pitocin.


From OBGYN.NET
By Myer S.Bornstein and Don Shuwarger

  1. The pregnancy should have completed 38 weeks or lung maturity; completed 36 weeks with a maternal or fetal indication for induction of labor;
  2. There should be an absence of acute fetal distress, abruptio placenta, placenta previa or unexplained vaginal bleeding;
  3. Misoprostol can be used with intact or ruptured membranes;
PROTOCOL 1 - VAGINAL DOSING PROTOCOL 2 - ORAL DOSING

In the papers reviewed the Misoprostol is inserted into the posterior vaginal fornix by speculum examination, and the Dinoprostone gel is inserted INTRA-CERVICALLY via speculum. UK practice would be digital insertion of either into posterior fornix - i.e.. VAGINALLY for both.

If no one out there ( US/UK/the world ! ) is using it regularly for induction of labour how safe, sensible and medico-legally sound is it for a unit with no research experience of Misoprostol to start using it ?

Finally, in the studies induction was only in nice low risk women, singleton, >36 weeks, vertex presentation and no uterine scar - we have lots of women that don't fulfill these criteria.

Now the questions !

Is anyone out there using the stuff regularly ?
What protocols do you use ?
What restrictions ?
How have you found it ?
Do you guys really put the Dinoprostone in the cervical canal ? (
Thought I'd read somewhere that is less effective than in the posterior fornix ! )


Yes. We routinely use this via a protocol instituted by the Ob/Gyn department at our hospital. Our hospital is a large, tertiary private hospital (I actually read it was the busiest private hospital in the U.S. last year, which explains my call schedule) with in-house anesthesiology coverage, in-house Ob/Gyn coverage (my partners and I), and an in-house perinatologist (the infamous Armando Fuentes).

I believe the protocol is something like: use only if Bishop's score is less than 7, there are fewer than 6 contractions per hour (it might be 10), baby vertex, no distress (etc.). Place 50 micrograms into post fornix every 4 hours until contractions greater than 6-10 per hour or labor ensues. Patients must be on continuous fetal monitoring.

All drugs and therapies have possible side effects, but this stuff has worked extremely well for us. Failed inductions are subjectively far less common. I have heard of one case of uterine rupture (prior c/s, large doses over 2 days for pregnancy termination in a patient with a 2nd-trimester, non-viable fetus). I have used this in the 3rd-trimester at least 30 times, and have never seen tachysystole (yes, I know, my time will come), known uterine rupture, or other major complications. Sometimes the induction will not work, but in most cases 1 or 2 doses is enough, and labor begins or dilatation ensues. I believe careful fetal monitoring is necessary since the literature does report tachysystole.

Don't use Dinoprostone very much. In fact, misoprostol is now the drug of choice for labor induction in our hospital, and other than a few folks who use prostaglandin gel (put in at night; patient comes back in a.m.), the overwhelming majority of Ob/Gyns around here will now bring patient to the labor unit in the morning, place the misoprostol, and "stand back" (just kidding)!


  1. We are using Misoprostol regularly for induction. My department loves it.
  2. We use the protocol that have been published on OBGYN.NET Web Page
  3. The restrictions are the same as pitocin, if you would use pitocin you can use Misoprostol.
  4. Let me give an example: a primip at 38 weeks with increasing PIH/Preeclampsia long closed cervix, was given 50 micg. at 5 p.m. Labor started by 10 p.m. Spontaneous Vaginal Delivery at 2:30 a.m. we have found if the patient does not respond to Misoprostol they will not respond to pitocin induction. These are the patients that get sectioned. we have had no tetanic contraction, a few with very close contractions but no fetal distress monitor patterns.

I do have concerns about higher doses and we don't know if the incidence of in utero meconium aspiration syndrome is increased or any other complication of labor induction for that matter. We've measured intrauterine contractile pressures after a single 50mcg dose of Misoprostol and have found them in the usual ranges. We place the medication in the posterior vagina. We repeat the doses in 6-8 hours if no effect.

We are having patients use this medication under an experimental protocol with a separate consent that outlines published reviews of the medication, as well as benefits and risks. The patient signs this form prior to induction.


I have been using regularly for over two years and have not used pitocin for induction in that time. Most recently I have been using oral dosing, which seems to me to be much more predictable than the intravaginal approach. The same clinical judgment of whether the patient is going to be more or less sensitive (i.e., the term patient with a dilated cervix more sensitive, the preterm with an unripe cervix less so) as is appropriate to the use of pitocin is applicable to the use of misoprostol.


The misoprostol protocol we currently use:

Contraindications:

  1. Bishop's score of 7 or greater.
  2. Contractions less than 10 minutes apart (i.e. more than 6 per hour).
  3. Multiparity with greater than 6 term deliveries.
  4. The usual stuff: prior classical c/s, undiagnosed bleeding, fetal distress, malpresentation, etc.

Usage:

  1. 25-50 micrograms to posterior fornix every 6-8 hours.
  2. Hold further doses if greater than 6 contractions per hour.
  3. Use continuous fetal monitoring.
  4. No more than 8 doses (I have never seen a patient get this many).
That's the main info. I hope this answers your questions!

I've suggested to the nurses on Labor and Delivery that the day will come when the OB/GYN lines up all of her/his 39 weekers on a Thursday. They have an early lunch followed by an NST in the office. If reactive, and all other criteria are met, they have 50 mcg Cytotec placed in the vagina in the late afternoon and head over to LandD. If all looks well they'll be sent home and asked to return when contractions are stronger, SROM, bleeding, etc.... The majority will return around 1am and deliver before outpatient surgery starts on Friday morning.

The nurses seem unenthusiastic about this plan, and Thursday night might be an experience, but it would certainly improve my attitude about the rest of the week!


My question for those who use cytotec on regular basis: If after the first dose the woman is contracting vigorously (Q 2 min) but no cervical change, do you go ahead with next scheduled dose every 4 hrs?


We are using it, and if the patient is in labor, with normal contractions we don't repeat the misoprostol. If needed we rupture the membranes. Most of the times you only need one dose. Sometimes the cervix doesn't change initially, but after a few hours becomes shorter and dilate very quickly.


I advise residents to skip repeat doses of Cytotec if the patient has palpable contractions greater than every 6 minutes on average. I think cytotec should be used as a ripening agent and not an agent to induce hard and regular contractions. @ 50mg/4h I have seen a lot of hyperstimulation and some acidotic babies. I usually recommend 30mg/3h for 3 dose, which was found to have less hyperstim and reasonable effectiveness.


I don't think it is wise to continue with further dose of cytotec if your patient is contracting in that manner as you are quite right that the risk of hyperstimulation is very high. From your findings, I think your patient did show some progress in cervical ripening. I have encountered a few cases where the cervix progressed from 1-2 cm to fully within less than 4 hours after 1-2 dose of cytotec.


Our protocol states that if the patient is contracting more than 6-8 (can't remember exactly which one) times per hour, she cannot have more misoprostol.


Misoprostol Protocol

  1. 50 micrograms in posterior fornix every 4 hours.
  2. Use continuous fetal monitoring.

Contraindications:

  1. Unexplained vaginal bleeding.
  2. Prior classical c/section or extensive myomectomy, anomaly repair, etc.
  3. Greater than 10 contractions/hour.
  4. Bishop's score greater than 7.
  5. Malpresentation, previa, etc. (any regular contraindication to induction).
  6. Relative: greater than 6 previous pregnancies.
We have used this, after informed consent, in patients with prior low transverse c/section. I have not heard of any uterine ruptures or other significant problems using this protocol, but we have had this for only about 6-8 months.

It has subjectively dramatically improved the time to delivery and induction success rate, and I'm waiting for the pregnant nurses to take some home to induce labor when they hit 38 weeks :)


We are still using cytotec Our dosing is 50 mcg q 4 hrs usually not needing more than two doses or 100mcs po times one dose. No major problems. If the patients doesn't response to cytotec we have also seen no response to other oxytocics and have led to c/s


I usually preferred to administer through vaginal route - no doubt there is no proven absorption and distribution rate studies that has been documented ( anyone had any paper on it ?). The advantages that I find personally is that I can VE the patient for progress of the labour at the same time , and sometimes when the labour contractions becomes too strong and tumultuous, the same tablet can be extracted out ( I usually used about 100 mcg dose in the vagina)easily and the contraction occasionally ceased. I wonder any of you have the same experience to share?


Don't know how many of you saw two papers on Misoprostol for labour induction in Am.J.Obstet.Gynecol. 1997; 89(4): ( April ):

Meta-analysis of all trial using Misoprostol v. Dinoprostone/Oxytocin/placebo

Sanchez-Ramos et al. pp633-642

RCT of Misoprostol v. Dinoprostone gel

Buser et al. pp581-5

They were reviewed in our departments Journal Club last week ( when I was on leave ). On the basis of these two papers one of my colleagues is suggesting we should go straight over to Misoprostol and obviously save vast amounts of money !

My problems are that:

The first study shows an increased CS rate in the Misoprostol group ( the other paper doesn't, but I view the results on that outcome as being so heterogeneous to warrant suspicion ).

The obvious explanation for superiority of Misoprostol is that it is either given in big doses or doses are repeated every 4 hours, whereas the Dinoprostone is only ever repeated 6hrly in studies.


We tend to continue the Cytotec until the pt has established a satisfactory labor pattern and is well into the accelerated phase of labor, (perhaps naively) relying on tocolytics to get us out of hyperstim (which hasn't happened to us yet). I have backed down to 25 mcg a couple of times, when the uterus looks a little too active.

My partner and I have done over a hundred oral misoprostol inductions since we started using Cytotec in March of this year. We use 50 mcg po q 4h, monitor continuously for 1 hr after each dose, then intermittently for the next three hours, feed the patient, without IV, (assuming there are no other indications for IV or IV med), until they are in the accelerated phase of labor, and ambulate them during the three hours they're intermittently monitored. I don't remember the last time we started an induction with pit. We do use pit occasionally to augment.

I used to avoid doing inductions with Bishop's scores less than 6 or so, and could never get enthusiastic about the cervical prostaglandins, but now I just schedule the induction, regardless of the cervix, and have had very good outcomes.

Our biggest fear is that the company will pull Cytotec from the market, since our internist/GI buddies tell us that it isn't worth a darn for its labeled indication.



Oral Dosing



Misoprostol Administered by Epithelial Routes: Drug Absorption and Uterine Response.
Meckstroth KR, Whitaker AK, Bertisch S, Goldberg AB, Darney PD.
Obstet Gynecol. 2006 Sep;108(3):582-590.

CONCLUSION: Although serum levels were lower for buccal compared with the vaginal routes, the three routes produced similar uterine tone and activity. Rectal administration produced lower uterine tone and activity. Vaginal serum levels were two to three and a half times higher than those observed in prior misoprostol pharmacokinetic studies. LEVEL OF EVIDENCE: II-1.


Oral misoprostol for induction of labour at term: randomised controlled trial.
Dodd JM, Crowther CA, Robinson JS.
BMJ. 2006 Feb 2; [Epub ahead of print]

CONCLUSIONS: This trial shows no evidence that oral misoprostol is superior to vaginal dinoprostone for induction of labour. However, it does not lead to poorer health outcomes for women or their infants, and oral treatment is preferred by women.


Slower absorption through oral use

A masked randomized comparison of oral and vaginal administration of misoprostol for labor induction.
Bennett KA, Butt K, Crane JM, Hutchens D, Young DC
Obstet Gynecol 1998 Oct;92(4 Pt 1):481-6
There is a shorter interval to vaginal birth with vaginal application; however, the more frequent occurrence of fetal heart rate graph abnormalities in this group suggests that, until the optimal dosing interval for vaginal use is determined, the preferred route of misoprostol administration might be oral.
Basically they found that the vaginal route worked much faster, but was associated with more tachysystole and hyperstimulation. All the babies were fine.

They quote someone who studied the pharmacokinetics of cytotec and found that vaginally administered, it had three times the systemic bioavailability of oral dosing.


Prostaglandins are absorbed 10X more efficiently through the gut than through the vaginal mucosa, with respect to semen and labour onset. Might it be possible that cytotec is more effective given orally than vaginally? And I am curious about whether the safety factor is affected by route of administration.


Spot on, there is a difference in absorption between routes. Various studies have been done/are underway to look at dosing differences by the two routes. Currently the evidence is you need less orally, but not so far convincing enough. An issue for us in UK is we only have a bigger dose available than you guys in USA, it might even be better for us to stick with the higher dose PV than the lower dose PO.


Dr. Maslow at the perinatology center in Tacoma prefers the po route, as there seems to be less uterine irritability and similar outcomes. He's got several supportive articles/protocols too. He's the one that does a NST in the office, gives the pill (50mcg) and sends the women out to come back in 4 hours. Claims >90% success with this, with no additional complications. I'd like to see comparisons of large vs. small women, and primips vs. multips.


I have been using oral for the last 2 pts, and found it worked well. When I give it intravaginally, I often find the softened pill just sitting there. Then when I rub it around the posterior fornix, she jump-kicks into really fast contx, which I don't much care for. Orally, the last 2 have been much more mellow, but still work.


The last 2 I did cytotec on I gave it orally. One because SROM, the other had Previous GBS septic baby. Both went into nice slow labor - one needed pit after 2 doses and no progress, but del w/i 6 hrs of starting pit. Big study. Pure anecdotal. but it does work orally.



Importance of Assessing Each Client



I think one of the big problems we are having establishing dosage of misoprostol is that the effective/over-effective dosage is dependent on the patient's characteristics. this includes cervical status, parity and gestational age, at least. in addition, after selection of the initial dosage in mcg., the important modulation may be in the dose interval rather than the amount of the drug.


Does it make any sense that one should adjust the dosage of Cytotec depending on the woman's body weight?


Someone talked about this at the Midwifery Today conference.  I can't recall the amounts, or at what weight you would increase the dose- its in my notes somewhere.  She also felt that obese women have a deficit in oxytocin- I can't remember if the reasoning was that they make the same amount as non-obese women but it is too diffuse in their body, or they make less oxytocin because they are obese.  She thought cytotec was a great thing for these ladies, and much less painful than a pit induction.


Not if given vaginally and probably not if given orally.  In it's on label use (ulcer prevention) there is no information about lipid binding and need to adjust for body size.


I would think it would depend on where you are putting it!  Intravaginally, I wouldn't think so, since it is being absorbed directly at the site of action; orally, maybe so since it must pass thru the liver, etc., to get where it's going.  Just my thoughts, I have no evidence (and I suspect no one else does yet) one way or the other.


The whole thing is totally uncontrolled, uncontrollable anyway. we don't even know why some tabs don't even dissolve, and are found just sitting in the vagina. ?ph? ?KY jelly? The dosage is made by crudely dividing a table into 1/2 or 1/4,,,,don't think it could get too terribly precise.


I don't think that has been studied at all. I think that the indivdual responsiveness to prostaglandins is more significant than weight.



Cytotec - Evenly Distributed in Tablet?



Another question - can one assume that the active ingredient is evenly and homogeneously distributed throughout the tablet? Is it possible that all the active ingredient can be in just one section of these little pills.


We have seen very variable results with cytotec. Some women do nothing, some have tumultuous labors. We use 25 mcgs q4h unless there are frequent contractions.

My question: since cytotec is a pill for oral use, can we be assured that the active ingredient is evenly distributed throughout the inert carrier?


The same question about distribution of the active ingredient when a tablet is quartered has come up in conversation here as well, we have just started using cytotec and have already seen lots of variable responses.

The latest green journal has an article about uterine rupture after the use of misoprostol in 25mg. doses q 4 hrs., hope this won't prove to be too much of a wild card to continue to use.


Maybe what we need to do is have the pharmacist grind the tabs into 4 cc of gel, and then divide it into 4 syringes (ala old days of home made prostin gel).



Cytotec for Homebirth



CAUTION - Homebirth use of Cytotec is very dangerous before the baby is born!  (It's fine for controlling bleeding after the baby is born!)

As a homebirth practitioner, I take the cautions of hospital midwives very seriously concerning the potential dangers of Cytotec, but have still chosen to present it as an option to clients on a few occasions when it seemed important to get labor going (when the usual arsenal of labor-starters had failed).

I tell clients up front that the use of Cytotec for this purpose is not FDA approved, nor is its use compatible with the local standard of care (as far as I know, it isn't being used by any hospital practitioners around this area). I explain that we don't have a lot of published data on the safety of the drug, and then share what my limited experience is (making sure they also understand that I'm talking truly limited). The risks are reviewed, particularly the possibility of tetanic contractions, but the studies I have read show no adverse fetal outcomes. My written protocols call for starting with a small test dose (like 25 mcg) first to determine a client's individual sensitivity to the drug.

So far, I've had only positive experiences with Cytotec - usually a few hours of lag time and then the onset of contractions that seem to very effectively dilate the softened cervix. Clients have been very pleased.

My sample is so tiny, though, and if adverse consequences happen only one out of every twenty times, it will take me forever (maybe) to even see one. That doesn't make that one any less important or likely. So I will probably continue to be very cautious, do as careful informed consent, and only offer the option is I feel that the indications are clear (not just "I'm tired of being pregnant - can't we get this going?" kind of thing). [Ed: This was NOT written by me, but by a midwife in a part of the world where this use is legal.]



Cytotec Anecdotes



Forced Labor - "Why are obstetricians speeding deliveries with an ulcer drug that endangers mothers and their babies?" from Mother Jones.


One of the precipitous births that we experienced, the pill came out on the baby's head. Obviously not dissolved -- of course she only had about a 1 hour labor -- primip -- since then we don't use as much. She was not in labor at all, no contractions, when we inserted the tablet.

We have had one very precipitous birth, and a couple of pretty fast ones. I have used it to successfully induce really hard cervixes, though, and very overdue clients. They were not precipitous at all. Labor stated right away, and I continued the cytotec every 4 hours or so, for 2 or 3 insertions. When labor was well under way, I quit. Clients had nice normal labors. I've been experimenting with using just a tiny little "crumb" of cytotec, not very scientific -- I know. I have had very good results. i have never had any bad heart tones, meconium, or low apgars, no hypertonic contractions -- seems a lot safer to me than pitocin. I think that if you start with a very small amount, and you are patient, that you can finally get labor going, and have a manageable, not precipitous labor. Clients also claim that labor doesn't hurt as much -- don't know if that is true or not, but have been told that several times -- my whole experience if very limited, though.


I have used cytotec a few times OOH and haven't seen the all-or-nothing response that Betsy describes... well, I have seen a "nothing" response. But the other times, I saw a latent period and then a nice labor, usually short, but not with the harsh abruptness of many Pit-induced labors I've seen. The moms have not felt overwhelmed and their contractions weren't overly long or close. I suspect that the shortness of the labor has to do with the incredible softness of the cervix that can result from the cytotec as well as stimulation of uterine activity.

Having said that, I have a great respect for others clinical experience and know there are some who have used Cytotec a lot more than I have and have good reason for their opinions. That's why I want to have a GOOD reason to use it and am very judicious about the doses I use. I give lengthy informed consent (which includes the lack of FDA approval and the uncertainty of response). I have prescriptive privileges, so can use the stuff legally. Those of you who are not licensed and do not have prescriptive privileges are certainly taking a bigger medical-legal risk by using a non-approved prescription drug at home in an attempt to induce labor. I'd advise extreme caution.


I DO NOT like the uncontrolled labors I have seen with cytotec, my lit search shows "uterine tachysystole" to occur in just about every study, regardless of the dose (25 to 100mcg) route (oral or vaginal), and frequency (q 3 to q 6 hours). What good does it do to induce labor rapidly and effectively if you end up sectioning a woman at 9 cms for fetal distress (and find an 80% abruption in the OR). I admit it, I'm scarred, because this is just what happened to the first lady I cared for on Cytotec (4 years ago now, when I was an L&D nurse). I'm also scared because of what I see as the hidden assumptions behind the "jump on the bandwagon" approach to Cytotec inductions. These are (in no particular order):

I have also seen community hospitals that don't think informed consent is needed before giving Cytotec.

And I am really concerned that it will start to be used in an unmonitored way by practitioners (from OBs to midwives to the women themselves) who don't believe that something so little can pack such a punch. I have been a student of the history of health care for most of my life. The path from then to now is littered with the corpses of good ideas with horrific outcomes. We have refined out a few nuggets, and even in the core of the worst tragedies there has been knowledge gained. Still, I think about retrolental fibroplasia, and DES, and amphetamines for weight control, and telling pregnant moms to only gain ten pounds. I think about the surgical fads, like sprinkling the beating heart with talcum powder, and routine tonsillectomy, and routine episiotomy. Thalidomide (which by the way is turning out to be a very valuable drug in the treatment of leprosy, and possibly even some cases of AIDS). The kids who got polio from the first, inadequately tested batch of vaccine. The soldiers infected with hepatitis in their Yellow Fever vaccine. And even more recently, moms I have seen in pulmonary edema from their tocolytics, or in SVT from the same drugs. So, yes, I'm wary. That doesn't mean that I wouldn't use cytotec. But it does mean that I would think long and hard about it, and I would involve the family in the decision as much as possible. But, of course, isn't that what midwives do anyhow?


I saw a PP woman today who was big-time unhappy re her experience with cytotec. She said she was 3cm-3cm-3cm-3cm X 24 hours, then delivered in 30 minutes. She was Muslim, came to our practice for female providers, and was attended by a male resident....there was no time to call the mw.

I can't explain why it seems to be all or nothing. Maybe it is the lubricant or placement of the tablet in the vagina.


[from ob-gyn-l]


We are looking for clinical experiences with misoprostol for labor induction or cervical ripening. Have read many studies but now are interested in what folks are finding in their clinical experiences. Have reviewed several protocols with varying dosages and routes of admission and wonder what is working for folks.

Our first attempt with induction went like this: A primip at 39 wks with mild PIH had an unfavorable cx. At 9am she got 50mcg of misoprostol vaginally. Repeated dose 2 more times 4 hours apart. FHTs reactive, BL 150's through out the day. 12 hours after the first dose she started having strong UCs q 2-3 minutes. She went from 2cm to delivery in less than 2 hours which resulted in some fetal distress. Vac Ext delivered 6# 13oz male infant apgars 3/8.

Are people giving it vaginally, orally?? and in what dosages? Anyone else finding rapid labors such as this one? Any protocols you might be willing to share?

G3, P2 with 2 previous cesareans. Decided to use Cytotec at 38 weeks to ripen cervix, induce labor and increase chances of vaginal birth.

Day 1: 4 doses of 50 mcg spaced 3 hours apart. No contractions. Day 2: 4 doses of 100 mcg spaced 3 hours apart. No contractions. Day 3: Waters broke and labor started in the middle of the night.

Uncomplicated vaginal birth within 12 hours.

Only recommendation is to allow more rest in between doses so that mother isn't so exhausted at birth.


The other article in the Green: I thought it would be interesting for the list because there has been so much talk about misoprostol:

So I guess it looks like we will ultimately be using it vaginally?

Actually, i suspect the more rapid absorption and degradation with oral administration to make use via this route more predictable. i have just about given up vaginal use in favor of oral because my clinical observation suggested more rapid onset and more predictability.


I agree. We have been very happy with using misoprostol orally (about 40 patients in our practice so far), especially since that route makes it usable and effective in PROM, etc. We HOPE the future lies in using in PO use at home (in patients who have a neg BPP and NST, etc.)


Does anyone have any sort of protocol for office use of misoprostol? In theory it sounds very attractive.


One of our physicians uses Misoprostol at home, sees them evaluates with a NST then give 100-200 mcgrams po and either they come back in active labor or return the next morning for pitocin.


Actually, i suspect the more rapid absorption and degradation with oral administration to make use via this route more predictable. i have just about given up vaginal use in favor of oral because my clinical observation suggested more rapid onset and more predictability.

 




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