Sunday, August 9, 2009


There's been some discussion and concern about my use of cytotec for an induction so just wanted to share some research about cytotec. Here are abstracts with references. Enjoy!

1. Abstract
Misoprostol (Cytotec) is safe and effective for induction of labor, although it is not approved by the Food and Drug Administration (FDA) for use in pregnancy. In August 2000, the manufacturer of misoprostol warned against its use in pregnancy because of its abortifacient properties and cited reports of maternal and fetal deaths when misoprostol was used to induce labor, fueling the misoprostol controversy. More than 45 randomized trials including more than 5400 women have found vaginal misoprostol to be more effective than oxytocin or vaginal prostaglandin E2 at effecting vaginal delivery within 24 hours. Cesarean delivery rates with vaginal misoprostol are lower than with oxytocin alone, but similar to prostaglandin E2. There have been no significant differences in the frequency of serious adverse maternal or neonatal outcomes with low-dose misoprostol compared with oxytocin or prostaglandin E2; however, the relative risk of rare adverse outcomes with misoprostol is unknown. The data suggest that absolute risks are low when misoprostol is used appropriately. We recommend 25 mcg vaginally every 4 to 6 hours for carefully selected patients in closely monitored settings. Whether misoprostol will prove to be the most cost-effective agent for inducing labor in women with an unfavorable cervix remains to be determined.

Induction of labor: the misoprostol controversy Alisa B. Goldberg, Deborah A. Wing Journal of Midwifery & Women's Health July 2003 (Vol. 48, Issue 4, Pages 244-248)

2. Misoprostol - a stable prostaglandin E1 analogue- is effective and safe in the induction of labour. There is paucity of information about the use of misoprostol for labour induction in Nigeria. OBJECTIVE: To evaluate the efficacy of misoprostol in the induction of labour in the third trimester. METHODS. Consecutive patients for induction of labour were randomized into misoprostol or oxytocin study groups. The misoprostol group received intravaginal 50 microg 6- hourly to a maximum of four doses. Those in the oxytocin group received a maximum of 48 iu/min. Outcome measures included induction-delivery interval, mode of delivery, Apgar score, perinatal death and maternal complications. RESULTS: Sixty-two patients were recruited into the study-34 received misoprostol while 28 received oxytocin. The modal gestational age and Bishop score prior at induction were >36 weeks and 5-7 respectively. Hypertension in pregnancy was the commonest indication for induction of labour followed by prolonged pregnancy. The overall induction-delivery interval was 12.2 +/- 5.2 hours; Misoprostol v oxytocin, mean(range): 12.1(7-27) vs 12.3(4-27) hours, p = 0.88). There were no significant differences in the mean Apgar score and perinatal mortality rate in the two study groups. There were two cases of primary postpartum haemorrhage in the oxytocin group but none in the misoprostol group. One case of ruptured uterus was encountered in the misoprostol group. No case of maternal mortality was recorded. Four patients in the misoprostol group had minor side effects mainly nausea and vomiting. CONCLUSION: The efficacy of misoprostol in the induction of third trimester labour is comparable to oxytocin. The risk of ruptured uterus associated with misoprostol appears higher than that of oxytocin in the induction of labour. Further studies are needed to verify this observation in our setting.

Efficacy and safety of misoprostol in induction of labour in a Nigerian tertiary hospital.
Abdul MA, Ibrahim UN, Yusuf MD, Musa H.
West Afr J Med. 2007 Jul-Sep;26(3):213-6.

3. BACKGROUND: Misoprostol (Cytotec, Searle) is a prostaglandin E1 analogue marketed for use in the prevention and treatment of peptic ulcer disease. It is inexpensive, easily stored at room temperature and has few systemic side effects. It is rapidly absorbed orally and vaginally. Although not registered for such use, misoprostol has been widely used for obstetric and gynaecological indications, such as induction of abortion and of labour. This is one of a series of reviews of methods of cervical ripening and labour induction using standardised methodology. OBJECTIVES: To determine the effects of vaginal misoprostol for third trimester cervical ripening or induction of labour. SEARCH STRATEGY: The Cochrane Pregnancy and Childbirth Group trials register (October 2002), the Cochrane Controlled Trials Register (The Cochrane Library, Issue 3, 2002) and bibliographies of relevant papers. SELECTION CRITERIA: The criteria for inclusion included the following: (1) clinical trials comparing vaginal misoprostol used for third trimester cervical ripening or labour induction with placebo/no treatment or other methods listed above it on a predefined list of labour induction methods; (2) random allocation to the treatment or control group; (3) adequate allocation concealment; (4) violations of allocated management not sufficient to materially affect conclusions; (5) clinically meaningful outcome measures reported; (6) data available for analysis according to the random allocation; (7) missing data insufficient to materially affect the conclusions. DATA COLLECTION AND ANALYSIS: A strategy was developed to deal with the large volume and complexity of trial data relating to labour induction. This involved a two-stage method of data extraction. The initial data extraction was done centrally, and incorporated into a series of primary reviews arranged by methods of induction of labour, following a standardised methodology. The data will be extracted from the primary reviews into a series of secondary reviews, arranged by category of woman. To avoid duplication of data in the primary reviews, the labour induction methods have been listed in a specific order, from one to 25. Each primary review includes comparisons between one of the methods (from two to 25) with only those methods above it on the list. MAIN RESULTS: Sixty-two trials have been included. Compared to placebo, misoprostol was associated with increased cervical ripening (relative risk of unfavourable or unchanged cervix after 12 to 24 hours with misoprostol 0.09, 95% confidence interval (CI) 0.03 to 0.24). It was also associated with reduced failure to achieve vaginal delivery within 24 hours (relative risk (RR) 0.36, 95% CI 0.19 to 0.68). Uterine hyperstimulation, without fetal heart rate changes, was increased (RR 11.7 95% CI 2.78 to 49). Compared with vaginal prostaglandin E2, intracervical prostaglandin E2 and oxytocin, vaginal misoprostol labour induction was associated with less epidural analgesia use, fewer failures to achieve vaginal delivery within 24 hours and more uterine hyperstimulation. Compared with vaginal or intracervical prostaglandin E2, oxytocin augmentation was less common, with misoprostol and meconium-stained liquor more common. Compared with intracervical prostaglandin E2, unchanged or unfavourable cervix after 12 to 24 hours was less common with misoprostol. Lower doses of misoprostol compared to higher doses were associated with more need for oxytocin augmentation, less uterine hyperstimulation, with and without fetal heart rate changes, and a non-significant trend to fewer admissions to neonatal intensive care unit. Use of a gel preparation of misoprostol versus tablet was associated with less hyperstimulation and more use of oxytocin and epidural analgesia. Information on women's views is conspicuously lacking. REVIEWER'S CONCLUSIONS: Vaginal misoprostol appears to be more effective than conventional methods of cervical ripening and labour induction. The apparent increase in uterine hyperstimulation is of concern. Doses not exceeding 25 mcg four-hourly of concern. Doses not exceeding 25 mcg four-hourly appeared to have similar effectiveness and risk of uterine hyperstimulation to conventional labour inducing methods.The studies reviewed were not large enough to exclude the possibility of rare but serious adverse events, particularly uterine rupture, which has been reported anecdotally following misoprostol use in women with and without previous caesarean section. The authors request information on cases of uterine rupture known to readers. Further research is needed to establish the ideal route of administration and dosage, and safety. Professional and governmental bodies should agree guidelines for the use of misoprostol, based on the best available evidence and local circumstances.

Cochrane Database 2003

4. OBJECTIVE: Our purpose was to compare vaginally administered misoprostol (Cytotec) with intravenous oxytocin for labor induction in women with premature rupture of membranes beyond 36 weeks' gestation. STUDY DESIGN: Two hundred subjects with rupture of membranes without labor were randomly assigned to receive vaginally administered misoprostol or intravenous oxytocin. Twenty-five micrograms of misoprostol (Cytotec) was placed in the posterior vaginal fornix. If cervical ripening (Bishop score of > or = 8 or cervical dilatation of > or = 3 cm) or active labor did not occur, a single repeat dose of misoprostol was given 6 hours later. Oxytocin was administered intravenously by a standardized incremental infusion protocol to a maximum dose of 22 mU per minute. RESULTS: Of the 197 subjects evaluated, 98 received misoprostol and 99 oxytocin. The average interval from start of induction to vaginal delivery was about 1 hour longer in the misoprostol group (811.5 +/- 511.4 minutes) than in the oxytocin group (747.0 +/- 448.0 minutes) (P = .65, log transformed data). Oxytocin administration was necessary in 37 of 98 (37.8%) of misoprostol-treated subjects. Vaginal delivery occurred in 85 misoprostol-treated subjects (86.7%) and 82 (85.9%) oxytocin-treated subjects (relative risk 1.17, 95% confidence interval 0.78 to 1.78, P = .45) with the remainder undergoing cesarean birth. There was no difference in the incidence of tachysystole (six or more uterine contractions in a 10-minute window for two consecutive 10-minute periods) or hypertonus between the two groups. There was no significant difference in frequency of abnormal fetal heart rate tracings between the two groups (29.6% in the misoprostol group and 28.9% in the oxytocin group, P = .91). Chorioamnionitis was diagnosed in 28 (28.6%) misoprostol-treated subjects and 26 (26.3%) oxytocin-treated subjects (P = .72, relative risk 1.06, 95% confidence interval 0.78 to 1.45). No significant differences were found in the incidence of fetal meconium (8.1% and 9.1%), 1- or 5-minute Apgar scores < 7 (11.0% and 10.2% of 1-minute Apgar scores, and 2.0% and 2.0% of 5-minute Apgar scores), neonatal resuscitation (24.5% and 27.6%), or admission to the neonatal intensive care unit (25.5% and 32.3%) between the two groups. CONCLUSIONS: Vaginal administration of misoprostol (Cytotec) is an effective alternative to oxytocin infusion for labor induction in women with premature rupture of the membranes near term. The incidence of untoward effects is similar with use of the two agents

Am J Obstet Gynecol. 1999 Jan;180(1 Pt 1):253-4

There's a lot more out there but frankly I was getting tired of weeding through it. The most common argument against the use of misoprostol is the risk of uterine rupture. So I guess I better stop doing VBACs also - after all there's a risk of uterine rupture with that too.


Jan Andrea said...

It's great that actual studies are being done, but I wish they'd done them before it had been used on women in the 1990s, with no studies and with those women as, effectively, guinea pigs. I guess that's my problem with it; that it is being recommended under very narrow circumstances is a plus, but of course there will be those who will see this as, "See? It's perfectly safe!" and use that as an excuse not to explain the risks to their patients. I've heard so many stories (first-hand) like that.

Ciarin said...

I absolutely agree with you on this being another example of a medical practice being used prior to any well-rounded research being done. It's right up there with EFM, enemas, shaving, etc in terms of people jumping the gun to use a practice without any sound research.

Labor Nurse, CNM said...

Here's the thing: I love misoprostol. I've used it for cervical ripening and post partum hemorrhage and find the results far superior.

Yes, it's horrible that miso was used by some cowboys out there and ended up causing awful results. The risk of uterine rupture with miso is in women who have had a prior c-section; so guess what? Stay away from miso (or perhaps all prostaglandins) for ripening or induction. The unfortunate part is that any women's health issue lags behind in science based research and this is one example. But since the early 1990s, very sound evidence has been presented, and FIGO even has standard dosing regimens that are considered very safe.

So when misoprostol is touted as evil, I think it can be easily pointed out quite the opposite. What was the evil in the case of this drug was it's misuse by some doctors who were performing experimental research without it being at all official.

Prisca: said...

thanks so much! appreciate the 411.

pinky said...

Ah here you go using actual facts and real studies, sh1t that is going to be unpopular.

Ciarin said...

Sorry Pinky! What the hell was I thinking!