Myometrial activity after local application of prostaglandin E2 for cervical ripening and term labor induction

Myometrial activity after local application of prostaglandin E2 for cervical ripening and term labor induction

Myometrial activity after local application of prostaglandin E2 for cervical ripening and term labor induction Lena Granstrom, MD,' Gunvor Ekman, MD: ...

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Myometrial activity after local application of prostaglandin E2 for cervical ripening and term labor induction Lena Granstrom, MD,' Gunvor Ekman, MD: and Ulf Ulmsten, MDb Danderyd and Uppala, Sweden Twelve pregnant women at term with unfavorable cervices (s5 points according to Bishop score) were given prostaglandin E2 for cervical priming and labor induction. Prostaglandin E2 was given in the following manner: 0.5 mg in gel strictly intracervically (n = 4), extraamniotically (n = 4), or prostaglandin E2 (4 mg) in gel vaginally (n = 4). The myometrial activity was registered over a period of 30 minutes before and at least 3 hours after gel application by means of an extraamniotic microtransducer catheter. After both extraamniotic and vaginal gel application, myometrial activity was significantly increased compared with intracervical application. All the women had favorable cervical states 6 hours after treatment and were delivered vaginally within 24 hours. All infants were delivered in good condition with 1-minute Apgar scores > 7. From these results we conclude that proper intracervical prostaglandin E2 gel application. in contrast to extraamniotic or vaginal application, induces cervical ripening without significant myometrial activity. Because careful intracervical application appears to avoid or minimize the risks of myometrial hyperstimulation. thiS technique should be considered particularly in women with unfavorable cervices and delicate fetuses. (AM J OBSTET GVNECOl 1990;162:691-4.)

Key words: Cervical priming, PGE", myometrial contractions, labor induction

Several studies have confirmed that local application of prostaglandins is an effective method for ripening of the cervix at term ."" However, unwanted myometrial contractions or hyperstimulation have been reported as side effects. 2. 6. 7 It is therefore important to study and quantify the risk for possible side effects that may jeopardize a delicate fetus. The purpose of this investigation was to evaluate both the risk of induction of unwanted myomerial contractions after local application of prostaglandin E2 (PGE,) gel and to identify a gel technique that minimizes this side effect.

Material and methods Twelve pregnant women at term with unfavorable cervices (Bishop score:55 points) participated in the study. They were allocated into three g-roups. Group A consisted of four women (Bishop sC()J'e:55 points) who were treated with PGE 2 (0.5 mg) in gel that was applied strictly within the cervical canal. 1 , Group B included four women, also with unfavorable From the Departments of Obs/etncs and Gynecology. Karolmska 111stl/utet. Dallderyd Hospilal. Datulayd: and Uppsala Unwemty Hosp!lal. Uppsala.' Supp01'ted b,v the Swedt;/t M edica l Rell'flrch CounCil (grants no 6856, 7479). Magnus Bergwall. Tore N1l.mn. and Allmanna BB FoundatIOns. Received jor pubilcation } ulle 15. 1989; reVISed September 21. 1989; accepted October 24. 1989. Repnnt requests: Lena Granstrom. MD. Department of Ob,tetncs and Gynecology. Karohnska Institutet. Danderyd Hospltal. S-182 88 Dandervd. Sweden. 611 117686 '

cervical states (Bishop score :55 points). These women were treated with PGE 2 (0.5 mg) in gel deliberately applied extraamniotically.' The last group of women (group C) consisting of four pregnant women at term who had unfavorable cervical states (Bishop score:55 points). They were given PGE. (4 mg) in gel applied in the posterior fornix of the vagina." The indications for induction of cervical priming and induction of labor were medical, such as preecla mpsia, suspected postmaturity, or fetal growth retardation. All women were primiparous with intact membranes and no spontaneous uterine contractions according to tocogra phic recordings. Ultrasonographic scans had been performed twice during the pregnancy to estimate correct gestational age and to exclude abnormalities, such as placenta previa, multiple pregnancy, or breech presentation. Relevant data of the patients are given in Table 1. Amniotomy was not done until labor was well established and the cervix dilated ~4 cm. Gel preparation. The PGE" gel (Cervi prost, Organon OSS, The Netherlands) originates from a cross-link starch powder industria lly mixed with PGE, in ethanol solution and lyophilized." Immediately before application. 2.0 ml of saline solution (extraamniotic or intracervical) or 3.0 ml saline solution (intravaginal) was added to the PGE" powder. A highly viscous, stickly gel was thus achieved within 30 seconds. The gel was applied through a plastic catheter 12 cm long as described previously. 1 691

692 Granstrom, Ekman, and Ulmsten

March 1990 Am J Obstet Gynecol

' - -_ _ .._TA_A_CE_A_V'_CA_l_ _...JIITRANSCERYtcAL .. EXTRAAMNIOTlcl .... , _ _ _"_T_A"_""_O_'N_A_l_ _-,

10

15

20

Time (minutes)

10

15

10

20

Tim. (minutes)

15

20

Time (minutes )

Fig. 1. Typical tracing illustrates myometrial activity registered by microtransducer catheter before and 30, 60, and 90 minutes after different gel applications. Table I. Twelve term pregnant women treated with local application of PGE2 for cervical priming, labor induction, or both

Age (yr) Mean Range Gestational age (wk) Mean Range Parity Original cervical score Mean Range

Group C

Group A (0.5 mg intracenncal(v)

Group B (0.5 mg extraamniotlcally)

(4 mg in gel vaginally)

25.5 24-29

28 19-39

25 22-26

41 40-42 0

41 40-42 0

41 40-42 0

3.5 3-4

4 3-5

4 3-5

For strictly intracervical application, the tip of the catheter was introduced close to the inner meatus. The gel (corresponding to a volume of approximately 2.5 ml) was then cautiously applied within the cervical canal while the catheter was slowly withdrawn. For extraamniotic gel application, the tip of the catheter was allowed to pass the internal meatus, after which the gel application was commenced. During vaginal application, the gel was introduced in the posterior fornix of the vagina. Irrespective of the mode of application, the catheter was immediately withdrawn after application. Pressure recording. For proper registration of myometrial activity, a flexible 2 mm thin microtransducer catheter (Geltec, Scotland) was applied extraamniotically via the cervical canal without rupturing the membranes. The recording section at the tip of the catheter was placed 2 to 3 cm above the internal meatus. The registrations started 30 minutes before and lasted for 4 to 5 hours after gel application. The recording technique has been described in detail elsewhere. 9

Results The effects on the myometrium and cervix after the three different gel applications are shown in Fig. 1. Stricly intracervical application of PGE 2 gel induced minimal myometrial activity, whereas significant uterine contractions were recorded almost immediately after extraamniotic application . After intravaginal gel application, regular uterine contractions were registered within 30 to 60 minutes. The myometrial activity calculated in Montevideo units is shown in Fig. 2. The activity after extraamniotic and intravaginal application was considerably more pronounced than after intracervical application. Cervical states improved in all women after gel application. No significant difference in this parameter was found within the three groups of patients at reexamination 5 to 6 hours after start of treatment. Induction-to-delivery time differed in the three groups of patients; the longest interval occurred after intravaginal application (l0 to 15 hours) and the shortest interval was after extraamniotic application (6 to 9

Myometrial activity after PGE 2

Volume 162 Number 3

693

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p
50

0 ~

o

o

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:

:

30

60

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90

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Fig. 2. The myometrial activity expressed in Montevideo units after intracervical (group A), extraamniotic (group B), and vaginal (group C) application of PGE, gel.

Table II. Results after treatment with local application of PGE" gel

Original mean cervical score Cervical score 5 hr after treatment Mean Range Labor-delivery time (hr) Mean Range No. of instrumental deliveries Cesarean section Ventouse

Group A (0.5 mg IntracenJlcally)

Group B (0 .5 mg extraammotlcally)

3.5

4.0

4.0

6 5-7

7 6-8

6 5-7

8 6-10

7 3-9

12 8-14

0 2

0 1

hours) . Six instrument-assisted deliveries were necessary and vacuum extractions were performed (Table II). No complications, such as rupture of the membranes, bleeding, or infections. were recorded after application of the catheter. All patients were delivered vaginally and all infants had I-minute Apgar scores > 7. Comment

It is evident from this investigation that strictly intracervical application of PGE" (0.5 mg) in a highly viscous gel avoids or minimizes the risk of inducing myometrial hyperstimulation. Conversely, such a risk seems to be present if a considerable amount of gel is allowed to escape into the extraamniotic space. It is imponant to note that vaginal gel application, considered an easy and safe procedure, induced significant myometrial activity within half an hour. Hence it may be concluded that if cervical priming is the primary goal of the PGE, gel application, a strictly intracervical application of a highly viscous gel is to be preferred. It must also be emphasized that this is a sophisticated

Group C (4 mg in gel vaginally)

0 3

procedure that requires a trained obstetrician; the gel application must also be done under strict visual control to avoid its escape into the extraamniotic space with the ensuing risk of myometrial hyperstimulation. It is likely that combined intracervical and extraamniotic PGE, gel application will prime the cervix and induce labor simultaneously, resulting in a shon induction-to-delivery time. After extraamniotic gel application, such a procedure may be hazardous in patients with delicate fetuses because of the risks of unwanted strong uterine contractions in the presence of an unripe cervix. Vaginal application of prostaglandins, which requires a higher dose of PGE, compared with the intracervical route, also induces an apparent myometrial activity; but the cervical priming effect does not seem to be superior to that obtained after strictly intracervical gel application. Moreover, the higher dose of PGE, increases the risk of gastrointestinal effects. 6 On the basis of our results from this investigation and our previous experiences, we conclude that strictly intracervical application of a highly viscous PGE" gel is

Granstrom, Ekman, and Ulmsten

to be preferred if uterine contractions or myometrial hyperactivity are to be avoided at cervical priming and labor induction. REFERENCES 1. Calder AA, Embrey MP, Tait T. Ripening of the cervix with extraamniotic prostaglandin E" in viscous gel before induction of labor. Br J Obstet Gynaecol 1977:84:264-68. 2. Shepherd JH, Benett MJ. Laurence D, Moore F. Sims CD. Prostaglandin vaginal suppositories: a simple and safe approach to the induction of labor. Obstet Gynecol 1981; 58:596-600. 3. MacKenzie IZ. Embrey MP. Cervical ripening with intravaginal prostaglandin E2 gel. Br Med.J 1977.2: 1381-4. 4. Ulmsten U, Wingerup L, Belfrage P. Ekman G, Wiq\'lst N. Intracervical application of prostaglandin gel for induction of term labor. Obstet Gynecol 1982;59:336-9.

March 1990

Am J Obstet Gynecol

5. Ekman-Ordeberg G , Uldbjerg N, Ulmsten U. Comparison of intravenous oxytocin and vaginal prostaglandin E2 gel in women with unripe cervices and premature rupture of the membranes. Obstet Gynecol 1985;66:307-10. 6. Khoo PPT, Kalshekar M, Jogee M, Elder MG. Induction oflabour with prostaglandin E2 vaginal tablets. Eur J Obstet Gynecol Reprod Bioi 1981; 11: 313-8. 7. Calder AA . Embrey MP. Hillier K. Extraamniotic prostaglandin E2 for the induction of labour at term. J Obstet Gynaecol Br Commonw 1974;81 :39-46. 8. Ulmsten U, Kirstein-Pedersen A, Stenberg P, Wingerup L. A new gel for intracervical application of prostaglandin E2. Acta Obstet Gynecol Scand I 979;84(suppl): 19-21. 9. Ulmsten U. Andersson K-E. Multichannel intrauterine pressure recording by means of micro-transducers. Acta Obstet Gynecol Scand 1979;58: 115-20.

Management of severe postpartum hemorrhage by intrauterine irrigation with prostaglandin E2 M. Reuben Peyser, MD, and Michael J. Kupfenninc, MD Tel

AVIV,

Israel

Continuous intrauterine irrigation with minute amounts of prostaglandin E2 was used in 22 patients with severe postpartum hemorrhage unmanageable by conventional therapy. Twenty-one women were treated because of uterine atonic hemorrhage and one because of late postpartum hemorrhage from subinvolution. A quick tetanic contraction of the uterine muscle with dramatic and sustained hemostasis was achieved in all patients. The therapeutic response was continuous and uninterrupted regardless of the predisposing factors for the hemorrhage or the hemodynamic condition of the patients. No side effects were observed. (AM J OaSTET GVNECOL 1990;162;694-6.)

Key words: Uterine atony, postpartum bleeding, prostaglandin E2 Postpartum hemorrhage, primarily uterine atony, is responsible for approximately 25 % of maternal deaths.' It demands immediate attention and treatment to restore homeostasis. Management consists of oxytocin and ergot therapy, blood replacement, man~al massage, and bimanual compression. However, these measures may fail. necessitating operation with ligation of the hypogastric arteries, hysterectomy, or both . In recent years prostaglandins F 2u and F2Q analogue and E, were introduced to overcome severe postpartum hemorrhage. These agents were administered intravenously, intramuscularly, directly to the myometrium. or vaginally. This article describes the successful use of From the Department of Obstetrio and Gynecology A. Serllll Maternity Ho spltal, Tel AvIV M edIcal Center. and The Sadder Srhool of Medlcme , Tel AvIV Umvenily Recewed for publlcatton Dc/abe' 2. 1989; accepted October 20, 1989. Reprint requests: M. Reuben Pey5er. MD, Serlm Matenl1ty Hospital. P.O.B. 7079. Tel AvIV 61-070. Israel. 611117614

694

prostaglandin E2 (PGE 2 ) by continuous intrauterine irrigation in 22 patients with intractable early or late postpartum hemorrhage .

Material and methods Severe postpartum hemorrhage was defined according to Hayashi et at.' when associated with (1) hypotension (a systolic or diastolic pressure drop of 30 mm Hg or more), (2) estimated blood loss of 1000 ml or more, (3) decrease in hemoglobin concentration of 3 gm/dl or more without transfusion or a decrease of 2 gm/dl with 500 ml blood transfusion. Twenty-two patients with severe postpartum hemorrhage were entered into the study after genital tract injury and retained placental fragments were ruled out. The predisposing factors for postpartum bleeding in these patients are shown in Table I. Twenty-one patients hemorrhaged as a result of uterine atony and one was bleeding 9 days post partum from subinvolution of the placental site. These patients did not respond to treat-