Induction of labor with intravaginal misorprostol in hypertensive pregnancy

Gİriş

Our purpose was to compare the safety and efficacy of intravaginal misoprostol versus intravenous oxytocin for induction of labor in hypertensive disorders of pregnancy.

Yöntem

 Twenty-one hypertensive pregmant women with indications for induction of labor and unfavorable cervices were randomly assigned to receive either intravaginal misoprostol or intravenous oxytocin. Misoprostol (50-100 meg) was placed in the posterior vaginal formix every 4 hour with the maximum 400 meg doses. It was not given after either spontaneous rupture of membranes or beginning of active labor. Oxytocin infusion followed an established routine. All patient had a medical indication for induction of labor, a single pregnancy, cephalic-vertex presentation,' no previous surgical scars on uterus, no contraindications for vaginal delivery, Bishop score below 5 and gestational age between 24-42 weeks

Bulgular

The average interval from start of induction to vaginal delivery was similar both misoprostol and oxytocin groups. Successful induction of labor was achieved in 54.1% of misoprostol treated women at a dose of 100 meg or less. Only two patients in misoprostol group necessitated labor augmentation with oxytocin.

Sonuç

intravaginal administration of misoprostol is safe, efficient and costeffective alternative to intravenous oxytocin infusion for induction of labor in hypertensive pregnancies. 

Anahtar Kelimeler

Hipertansiyon, gebelik, eylem.indüksiyonu, misoprostol, oksitosin

Giriş

Misoprostol, a synthetic PGE1 analogue, is a gast- ric eytoproteetive agent that used for the pre- vention of gastric ulcers. Recently several investigati- ons have described the use of a misoprostol for perin- duction cervical ripening and labor induction (1-3). misoprostol is inexpensive and easy to administer, be- cause it is placed in the vagina, not the cervix. Re- cently, it was reported that vaginal misoprostol may be as effective as oxytocin for inducing labor with a living fetus (1,4).
Preeclampsia and eclampsia are life-threatening di- sorders of pregnancy and they still remain as an important cause of maternal and fetal mortality and mor- bidity (5,6). In cases with severe preeclampsia and ec- lampsia the definitive treatment is termination of preg- nancy after the patient has been stabilized (5). The in- duction of labor is difficult and risky, because of the- se patients are often far from term and mostly have unfavorable cervix (7). so, cervical ripening and labor induction are especially important in hypertensive pregnancy. In our clinic trial we have used misopros- tol successfully and we decided to publish it. This study was undertaken to compare the safety and efficacy of misoprostol with oxytocin used for la- bor induction in hypertensive disorders of pregnancy.

Yöntem

Twenty-one hypertensive pregnant women with intact membrane and unfavorable cervices (Bishop score<5) were included to study, after hospitalization all patients were evaluated by physical and pelvic exa- mination and laboratory evaluation was immediately performed. Treatments were commenced according to usual protocol. All patients except two mild preec- lamptic cases were received magnesium-sulfate treat- ment. Fetal status was determined by ultrasonography and external fetal monitorization.
If the blood pressure was higher than 160/110 mmHg, accompanied by either generalized edema or proteinuria (of at least 3 or more) on dipstick exami- nation, severe preeclampsia was diagnosed. Eclampsia is diagnosed if there is seizure that can not be attribu- ted to other causes in a preeclamptic patient.
Among the 21 hypertensive pregnant women 11 were randomly assigned to receive intravaginal misop- rostol and 10 were assigned to receive intravenous oxytocin. After admission and selection for the study half (100 meg) or quarter (50 meg) tablet of misopros- tol was introduced into the vaginal posterior fornix. If the patient far from term 100 meg dose was preferred. In contrast if the patient near to term 50 meg dose was preferred. If the patient was not in labor, the dose was repeated every four hour for up to maximum 400 meg doses, until effective uterine contractions and cervical dilatation were obtained. Vital signs, uterine contracti- ons and, side effects were monitored every 30 minu- tes. All women monitored by external cardiotocog- raphy after the application and continued intermit- tenly to the delivery.
Oxytocin was started at 4 mU/min and was gradu- ally increased in dose increments of 2 mU/mim to a maximum of 40 mU/min at 30 minutes intervals as ne- eded to achieve an adequate contraction pattern. Cri- teria for enrollment included the following; (1) absen- ce of active labor or fetal distress, (2) no previous ce- sarean delivery or other type of uterine surgery, (3) singleton pregnancy with vertex presentation, and (4) no contraindication to vaginal delivery.
Bishop score was evaluated before the treatment was started in all women and repeats Bishop scores were assigned before the administration of a subsequ- ent dose of misoprostol. Patients who have no adequ- ate contractile pattern and progress on cervical dilata- tion received intravenous oxytocin augmentation. Am- niotomy was not undertaken until the cervix was dila- ted >4 cm. Cesarean section was performed in two ca- ses in misoprostol group and one case in oxytocin group and the indications were rapid deterioration of maternal status and arrest of labor. These cases were not included to the study. Labor induction was consi- dered successful if the women delivered within 24 ho- urs of initiating misoprostol.
Statistical analyses were performed with the x2, student t and, Fisher's exact tests where appropriate. The significance level was p<0.05.
 

Bulgular

Totally 21 patients with preeclampsia and eclamp- sia were included to the study. Three patients in mi- soprostol group and, 4 patients in oxytocin group we- re nullipar and the others were multipar. Gestational age ranged from 24 to 42 weeks in misoprostol group and from 31 to 39 in oxytocin group. Gestational age was below the 32 weeks in 3 patients in misoprostol group and, in 2 patients in oxytocin group.
The distributions of patient's age, gravidity and gestational age were similar in the misoprostol and oxytocin groups (Table 1). Likewise, indications for la- bor induction were similar in both groups, bishop sco- re was less than 5 in the all patients and there were si- milar in both groups. Bishop score was less than 5 in the all patients and there were no significant differen- ce between misoprostol group and oxytocin group according to Bishop score (2.0+1.2 versus 2.4±1.1).Two women in misoprostol group had Hellp syndrome while being induced. Also there were 3 intrauterine death in oxytocin group and 2 in misoprostol groups.
Bishop score was less than 5 in the all patients and there were no significant differen- ce between misoprostol group and oxytocin group according to Bishop score (2.0+1.2 versus 2.4±1.1).
Two women in misoprostol group had Hellp syndrome while being induced. Also there were 3 intrauterine death in oxytocin group and 2 in misoprostol gro- up. The interval from initiation of induction to vaginal delivery was similar in both groups (6.2±3.9 versus 7.2±3.3, p>0.05). All patients were delivered within the first 16 hours. The in- terval from initiation of active labor to delivery was shorter in the misoprostol group but this did not reach statistical significance (5.1±3.9 versus 8.0±4.7, p>0.05). Successful induction of labor was achieved in 54.1% of misoprostol treated women at a dose of 100 meg or less and all these women only a single dose were app- lied.
The mean 5th minute Apgar score was lower in the oxytocin group than in misoprostol group (6.3±3-6 versus 7.3±3-2) but this difference was not statistically significant. The first minute Apgar score was below 7 in 4 patients in both groups. The distribution of comp- lications in both groups was similar. There were one partus precipitatus (interval from active labor to deli- very was shorter than 3 hours) and one vaginal lace- ration in misoprostol group and one cervical lacerati- on and two second degree perineal lacerations in oxy- tocin group. Fetal distress was detected as evidenced by the presence of meconium stained amniotic fluid or fetal tachycardia. There were two fetal distress ca- ses in both groups. There were two infant deaths in misoprostol group and one in oxytocin group after de- livery.
Oxytocin augmentation was used in two patients in the misoprostol group because of there were not adequate uterine contraction and progress on cervical dilatation. There were no significant changes in mater- nal vital signs in both groups. There was no serious maternal side effect in both groups, signs of hyperac- tivity sweating, fever, diarrhea or other gastrointestinal effects were not detected in misoprostol group. No uterine hyperstimulation were seen in both groups.

Tartışma

Prostaglandins have been used for labor induction for over 20 years (8). Misoprostol, a synthetic PGEl analogue, is a gastric cytoprotective agent that used for the prevention of peptic ulcers. It has been shown that PGE2 is succesful in the labor induction of preec- lamptic women (5,9). Also it has been reported that misoprostol effectively induces labor while causing few maternal side effects and ap- parently no adverse effects on the newborn (1-3,10). It was reported that vaginal misoprostol may be as effective as oxytocin for inducing labor with a living fetus (1,4). In this study the ad- ministration of misoprostol (50 meg or 100 meg), intravaginally proved to be as effective as oxy- tocin for inducing labor in hypertensive pregnancies. Misoprostol therapy was associated with less need for oxytocin and only two patients in misoprostol group necessitated labor augmentation with oxytocin.
Successful induction of labor was achieved in 54.1% of misoprostol treated women at a dose of 100 meg or less and, all these women received only one dose. Sanchez-Ramos et al (1), reported that three qu- arters of the patients in the misoprostol group requ- ired only one half tablet (100 meg). They concluded that possible advantages of misoprostol may be its du- al role in cervical ripening and labor induction.
Complications were minimal in the misoprostol group and were not significantly different from the oxytocin group. Maternal side effects of misoprostol such as sweating, fever, diarrhea was not detected in misoprostol group. No uterine hypersitumulation we- re seen. This study was hampered by inconsistent use of cardiotocography. Most patients were monitored by auscultation and palpation. So, subtle change in fetal heart rate and uterine contractions could have gone undetected. Apgar score was below 1 in A patients in both groups but two of them in each group were di- agnosed before delivery. There were 5 stillbirth in study group and two infants died after delivery in mi- soprostol group and one infant died in oxytocin gro- up after delivery. In our region hypertensive disorders of pregnancy are common and, they generally belong to low socioeconomic level and have no adequate an- tenatal care. So these patients usually admit to hospi- tal lately. We concluded that the increased complica- tions such as low Apgar score, increased stillbirth and fetal death related to these factors not to type of in- duction.
Recently Kailasam at al (11), reported that, when misoprostol was given 400 meg by orally, there was a modest decrease in mean arterial pressure 20 minutes after the dose, accompanied by a decrease in systemic vascular resistance and a compensatory rise in cardiac output and heart rate, so, misoprostol may positive ef- fect on blood pressure on hypertensive pregnant and this concern needs further evaluation.
As reported before cost of misoprostol is not expensive, it does not require refrigeration and also it does not require the continuous supervision deman- ded by an oxytocin drip (10,12). As previous investi- gators have indicated these all advantages of misop- rostol are especially important in developing countries. On the basis of this preliminary findings misopros- tol appear to as effective as oxytocin for inducing la- bor in hypertensive pregnancies. Misoprostol is cheap, effective, safe and easy to administer and it may posi- tive effect on blood pressure. These advantages of mi- soprostol are especially important for places that have insufficient health care, such as our region. In spite of the effectiveness of misoprostol evident in this preli- minary report there is need for further evaluation especially connected with safety and more suitable dose of misoprostol.

Sonuç

On the basis of this preliminary findings misopros- tol appear to as effective as oxytocin for inducing la- bor in hypertensive pregnancies. Misoprostol is cheap, effective, safe and easy to administer and it may posi- tive effect on blood pressure. These advantages of mi- soprostol are especially important for places that have insufficient health care, such as our region. In spite of the effectiveness of misoprostol evident in this preli- minary report there is need for further evaluation es- pecially connected with safety and more suitable do- se of misoprostol.



 

Kaynaklar

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2. Fletcher HM, Mitchell S, Simeon D, Frederick J, Brown D: Intra- vaginal misoprostol as a cervical ripening agent. Br J Obstet Gynaecol, 100:641-4, 1993.
3. Fletcher H, Mitchell S, Frederick J, Simeon D, Brown D: uitra- vaginal Misoprostol Versus Dinoprostone As Cervical Ripening and Labor-Inducing Agents. Obstet Gynecol, 83:244-7, 1994.
4. Margoulies M, Perez CG, Voto LS: Misoprostol to induce labor (Letter). Lancet, 339:64, 1992.
5. Roberts JM: Pregnancy related hypertension. In: Pedersen D, (ed): Maternal fetal Medicine: Principles and Practice. Philadelp- hia: WB. Saunders Company, 777-823, 1989.
6. Fadigan AB, Sealy DP, Schneider EF: Preeclampsia: progress and puzzle. Am Fam Physician, 49:849-56, 1994.
7. Taner CE, Hakverdi AU: Hygroscopic cervical dilators in ec- lampsia. Int J Gynecol Obstet, 41:283-4, 1993.
8. Poulsen HK, moUer LK, Westergaard AG, Thomsen SG, Giers- son RT, Arngrimsson R: Open randomized comparison of pros- taglandin E2 given by intracervical gel or vagitory for preinduc- tion cervical ripening and induction of labor. Acta obstet Gyne- col Scand, 70:549-53, 1991.
9. danışman N, Vicdan K, Ozmen Ş, Yapar EG, Gökmen O: Pros- taglandin E2 Gel in Patients With Severe Preeclampsia and Ec- lampsia. Gynecol Obstet Reprod Med, 1:102-105, 1995.
10. Bugalho A, Bique C, Machungo F, Faundes A: Induction of la- bor with intravaginal misoprostol in intrauterine fetal death. Am J Obstet Gynecol, 171:538-41, 1994.
11. KailasamMT, Lin MC, Cervenka JH et al: Effects of an oral pros- taglandin El agonist on blood pressure and its determinants in essential hypertension. J Hum Hypertens, 8:515-20, 1994.
12. Wing DA, Jones MM, Rahall A, Goodwin TM, Paul RH: A com- parison of misoprostol and prostaglandin E2 gel for preinducti- on cervical ripening and labor induction. Am J Obstet Gynecol, 172:1804-10, 1995.

	Dosya / Açıklama
	Tablo 1. Demographic characteristics of patiens and indicating for labor induction
	Tablo 2 Labor and delivery outcomes and Apgar scores