PROSTAGLANDINS

TERMINATION OF PREGNANCY IN CASES LITER0 BY

A.

INTRAVENOUS

P. Lange,

PROSTAGLANDIN

N. J. Secher

and

OF FETAL

DEATH

IN

Fza

J. Westergaard.

The Department of Obstetrics and Hospital, Odense,Denmark and the Sonderborg trics and Gynecology, derborg, Denmark.

Gynecology, University Department of ObsteCounty Hospital, Son-

ABSTRACT Delivery was induced by an intravenous infusion of prostaglandin F2,. (PGFzc,) in gradually increasing doses in 30 consecutive cases of fetal death in utero after the 28th week of gestation. Twenty patients delivered during the first day of prostaglandin administration, 9 on the second day, and 1 patient not until the third day of infusion. It is concluded, that intravenous PGF2, appears to be superior to oxytocin in termination of pregnancy under these conditions.

ACKNOWLEDGEMENT AB ASTRA, glandin F2cr.

Sweden,

has

kindly

provided

the

prosta-

l-9-76

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PROSTAGLANDINS

INTRODUCTION In comparative studies with oxytocin and prostaof these agents for induction glandin F2, the efficacy of labor at or near term is generally comparable (1,2, uterine response of prostaglandins is 394). However, less influenced by the duration of pregnancy (5), therefore the prostaglandins may be the drug of choice in the induction of labor in cases of fetal death in utero during the third trimester. The purpose of this study is to examine the efficacy of prostaglandin F2cL administered intravenously for induction of labor in 30 consecutive cases of late fetal death. PATIENTS

AND

METHODS

Late fetal death was defined as fetal death in utero during the third trimester of pregnancy. The patients included in this study were between the 28th and 40th week of gestation as estimated from the last menstrual of pregperiod, mean 33.0 weeks. The parity and duration of intrauterine nancy are listed in table 1. The duration demise ranged from 1 to 35 days, mean 7.8 days. The fetal weight varied from 440 to 3000 grams, mean 1439 f 60.7 grams.

Weeks of GESTATION

102

X- PARA

Total

28 - 30

2

8

10

31 - 33

2

1

3

34 - 36

5

7

12

37-40

1

4

5

10

20

30

Total

Table

0-PARA

1. Patient

population

by parity

and

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1976

age.

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PROSTAGLANDINS

A sterile vaginal examination was performed showing that the cervix was uneffaced and without dilatation in all patients before induction of labor. There were no signs of labor or ruptured membranes in any of the cases. The patient was placed in bed and an intravenous infusion was started. A sterile solution of PGF2, in a concentration of 10 ug/ml in 5% dextrose in water, was infused starting at a rate of 5 to 10 pg/min. The infusion rate was increased by 5 to 10 ug/min every 30 to 60 minutes, until adequate uterine contractions were observed. The infusion rate was then maintained until the third stage of labor. When labor was well established and the cervix dilated more than 3 cm, the membranes were ruptured artificially. Maternal pulse and blood pressure were monitored at regular intervals and all side effects were recorded. None of the patients received prophylactic antiemetic or antidiarrhoea medication. Uterine activity was monitored by abdominal palpation performed by midwives. If no or only slight progress in the cervix conditions was obtained after eight hours, the infusion was stopped and re-established the following day. RESULTS In the present investigation labor was induced in all 30 patients with late intrauterine demise by intravenous infusion of PGF2,. Twenty patients, 66,7%, delivered on the first day of prostaglandin infusion and 9 on the second day. One patient was not delivered until the third day. In this patient the concentration of PGF2, administered on the first day of infusion was a maximum of 20 ug/min, and this dose rate was too low to produce palpable uterine contractions. When amniotomy was performed all patients were delivered the same day. The length of PGF2c, infusion ranged from 3.5 to 31 hours, mean 10.4 ?r 5.8 hours (figure 1). The total dose of PGF2c( administered was from 3 to 70 mg, mean 15.1 mg. The mean maximum infusion rate of PGF2, was 37.5 uglmin, range 15 to 90 ug/min, but only 3 patients in this study required an infusion rate of more than 45 vg/min. A negative significant correlation was found between the duration of the infusion and the length of gestation at the time of the procedure (r: I 0.40, p < 0.05) (Figure 1). However, there was no significant correlation between fetal weight and either the duration of PGF2, infusion (r: I 0.26) or the total dose of prostaglandin (r: I 0.21). One patient in this series delivered twins and 2 patients delivered anencephalic fetuses. Five other fetuses delivered were found to have congenital malformations.

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10.7

PROSTAGLANDINS

0

: 20

30 WEEKS

Figure

1.

35 OF

I 40

GESTATION

A negative correlation the infusion-delivery gestation.

was time

observed between and the weeks of

One of the pregnancies was complicated by severe hyThis patient pertension with superimposed pre-eclampsia. with an intrawas delivered in the 30th week of pregnancy uterine demise of 2 days duration. The patient had been treated with bed rest and antihypertensive drugs. The patient's infusion was 230/140 mm Hg, blood pressure prior to the PGF in ? usion the pressure fell to and during the prostaglandin headache 180/100 mm Hg. The patient stated that a pronounced had also been alleviated during the prostaglandin infusion. There was only a minimal change in pulse rate during prostaThe changes in blood pressure before, glandin administration. in this patient are during, and after PGF2, administration illustrated in figure 2. The other patients in this series were essentially normotensive, and intravenous PGF2, infusion produced no pronounced changes in either blood pressure or pulse rate. Uterine activity stopped, in general, within 1 to 2 hours after discontinuation of the PGF2, infusion in patients, who did not deliver during the first day of prostaglandin administration. There were two exceptions. In 2 patients, labor continued and these patients delivered 8 and 12 hours after discontinuation of the PGFzc( infusion. The infusion was discontinued in one patient due to vomit-

104

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PROSTAGLANDINS

I”

250

E p 3 R

200

g

IS0

8 2

100

50

0

Figure

2.

The blood pressure changes in a patient with hypertension and superimposed pre-eclampsia and after the intravenous before, during, infusion of PGF2c(.

labor had been established in ing and diarrhoea. However, this patient and she was delivered using intravenous oxytocin 90 minutes later. This patient was nauseous before infusion, induction and the vomiting continued after the prostaglandin The other 29 patients in this study experienced infusion. either no or only mild side effects, mainly nausea. Five patients had episodes of vomiting and a single patient had phlebitis diarrhoea to a mild degree. A mild, superficial was noted occasionally at the infusion site, when the needle had not been introduced into a large arm vein. One patient experienced vaginal bleeding with an estimated blood loss of 1000 cc due to a laceration of the cervix. In the other patients the estimated blood loss was less than complications associated with 500 cc. There were no further intravenou; PGP2cr :_z.._:^_ Sei*ieS ijf 30 paiieiiij. I ,I ihiS III1us l",, I-

DISCUSSION The treatment of patients with known intrauterine demise is a matter of contraversy. In the majority of cases the patients will deliver spontaneof intrauterine demise, ously within 2 to 3 weeks (6), but this approach submits

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the patient to mental distress and exposes her to the risk of infection and coagulation disorders (7). At the present time the treatment of choice has been intravenous infusion of high concentration of oxytocin, which has met with varying degrees of succes. Surgical induction of labor by artificial rupture of the fetal membranes carries a serious risk of uterine infection. Karim (8) has administered intravenous infusion of prostaglandin E2 (PGE2) to 15 patients with intrauterine demise. Thirteen patients delivered during the first day and one patient delivered on the second day of infusion. Beazley and Gillespie (9) reported that labor was successfully induced by intravenous PGE2 in 5 of 8 patients with intrauterine death.

In 7 patients with late fetal death in utero, Karim et al. (lo), successfully induced delivery in 6 patients the first day, and 1 patient the second day with a constant intravenous infusion of PGF2 at a rate of 0,05 vg/kg body weight/min. Pedersen et al. 711) administered a maximal infusion rate of 60 to 90 pg PGF2,/min to 9 patients with intrauterine demise after 28th weeks of pregnancy. Six patients delivered during the first day and 3 the second day. Frumar et al. (12) reported on 5 cases of intrauterine demise in which pregnancy was terminated by intra-amniotic instillation of PGF These authors instilled the PGF2c, intra-amniotically pa* rom 1 to 3 times with successful termination of pregnancy in all cases. Intra-amniotic administration of PGF as compared with intravenous infusion, is associated wit ia a lower incidence of gastro-intestinal side effects and a decrease in severity of these and other side effects. in the third trimester, intra-amniotic inHowever, stillation of prostaglandin may expose the patients to a as is the case in the second tririsk of uterine rupture, it is difficult to determine the exmester (13), because required for successful inductact dose of prostaglandin, ion in each patient. Therefore we consider the intravenous route of prostaglandin administration safer in cases of late intrauterine demise, since it is possible to decrease or discontinue the infusion with immediate effect in case of hypertonic contractions. infusion in The side effects of intravenous PGF2 our series were minimal as correlated wit! those, reported by other investigators. The PGF2, infusion had to be terminated in only one patient due to gastro-intestinal disturbances. We feel that the infusion rate employed study, mean 37.5 vg/min, was too low in some 106

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in this present cases, and a

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PROSTAGLANDINS

higher infusion rate of PGF in these improved our results, proba zl ?y without in the incidence of side effects.

cases would a noteworthy

have increase

Hypertension associated with intravenous infusion of oxytocin in high doses has been reported (14), while PGF2, has been shown to have little or no effect on blood pressure in normotensive patients (15). In our series, a patient with hypertension and superimposed pre-eclampsia experienced a fall in blood pressure and the disappearance of subjective symptoms during PGF2c, infusion. As far as is known, this is the first report of a patient suffering from hypertension, who experienced such a pronounced fall in blood pressure during PGF20 administration. Allthough a controlled clinical trial has not been performed, it is our impression that intravenous PGF2c, infusion is superior to oxytocin in termination of pregnancy in cases of late fetal death in utero prior to term. REFERENCES 1. Andersen, G.G., J.C. Hobbins, and L. Speroff. Intravenous prostaglandins E2 and F2 for the induction of term labor. Am. J. Obstet. Gynecol. ?12:382, 1972. 2. Brown, A.A., J.D. Hamlett, 8.M. Hibbard and P.D. Howe. Induction of labor by amniotomy and intravenous infusions of oxytocic drugs - A comparison between prostaglandins and oxytocin. J. Obstet. Gynaecol. Br. Commonw. 80:111, 1973. 3. Spellacy, W.N., S.A.Gall, A.B. Shevach, The induction of labor at term. Obstet. 1973. 4. Vakhariya, induction

V.R., and A.I. Sherman, of labor. Am. J. Obstet.

and K.K. Gynecol.

Holsinger. 41:14,

Prostaglandin F for Gynecol. 113:21 K: 1972.

5. Wiquist, N., and M. Bygdeman. Induction abortion with intravenous prostaglandin 889, 1970.

of therapeutic F2cr. Lancet I:

6. Tricomi, V., and Obstet. Gynecol.

in utero.

S.G. Kohl. Fetal 74:1092, 1957.

death

Am.

J.

7. Pritchard, J.A., and O.D. Ratnoff. Studies of fibrinogen and other hemostatic factors in women with intrauterine death and delayed delivery. Surg. Gynecol. Obstet. 101:467, 8.

1955.

Karim, S.M.M. Use of prostaglandin of missed abortion, missed labor, Br. Med. J. 3:196, 1970.

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PROSTAGLANDINS

9. Beazley, J.M., prostaglandin Lancet 1:152,

and A. Gillespie. Double-blind trial of E and oxytocin in induction of labour. ,671.

10.

Karim, S.M.M., R.R. Trussell, K. Hillier, and R.C. Patel. Induction of labour with prostaglandin Fea, J. Obstet, Gynaecol. Br. Commonw. 76:769, 1969.

11.

Pedersen. P.H., J.F. Larsen, and B. Sorensen. Induction of labor with prostaglandin F2@ in missed abortion, fetus mortuus, and anencephalia. Prostaglandins 2:135, 1972.

12.

Frumar, A.M., I.D. Smith, and A.R. Korda. Prostaglandin of labor in pregnancies complicated F2a. for the induction by intrauterine death, anencephaly, and chromosomal anomaly. Prostaglandins 6:125, 1974.

13.

Karim. S.M.M., and S.S. ion. Br. Med. J. 4:161,

14.

Bieniarz, J., in Oxytocin. Heller, Editors). Pergamon

15.

Fishburne, J.I., W.E. Brenner, J.T. Braaksma, L.G. R.A. Mueller, J.L. Hoffer, and C.H. Hendricks. Staurovsky, Cardiovascular and respiratory responses to intravenous infusion of prostaglandin F2c( in the pregnant woman. Am. J. Obstet. Gynecol. 114:765, 1972.

108

Ratnam. 1974.

Mid-trimester

Terminat-

(R. Caldeyro-Barcia press, Oxford, 1961

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Termination of pregnancy in cases of fetal death in utero by intravenous prostaglandin F2alpha.

Delivery was induced by an intravenous infusion of prostaglandin F2alpha (PGF2alpha) in gradually increasing doses in 30 consecutive cases of fetal de...
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