Acta Obstet Gynecol Scand 58: 121-122, 1979
SHORT COMMUNICATION
THE EFFECT O F INDOMETHACIN ON THE INSTILLATIONABORTION INTERVAL IN RIVANOL-INDUCED MID-TRIMESTER ABORTION Anders Olund From the Department of Obstetrics and Gynecology, Karolinska instituter, Huddinge University Hospital, Huddinge, Sweden
Extra-amniotic instillation of Rivanol for the induction of mid-trimester abortion is a safe and effective method and its clinical value has been described in several reports (for ref. see (5)). The mechanism by which Rivanol induces abortion is, however, still obscure. It has been proposed that hypertonic saline induces abortion by stimulating the release of endogenous PGF2a (1). The fact that prostaglandin synthetase inhibitors prolong the inductionabortion interval in saline-induced abortion lends further support to this theory (4). The purpose of the present study was to examine possible effects of indomethacin, a strong prostaglandin synthetase inhibitor, on mid-trimester abortion induced by Rivanol.
MATERIAL AND METHODS Twenty women were included in the indomethacin group and 55 women in a control group who were admitted to the hospital for legal abortion during the period 1975-1977. The mean gestational age ( + I S.D.) was 16.1k2.7 weeks in the indomethacin group and 15.6f2.1 weeks in the control group. In all cases the abortion was induced by extra-amniotic instillation of Rivanol. A Foley balloon-catheter no. 20 was introduced into the extra-ovular space via the cervical canal. The tip of the catheter was placed just inside the internal 0s of the cervix and the balloon was filled with 30 ml of physiological saline. A 0.1 % solution of Rivanol was then slowly instilled, 10 ml per gestational week, but never more than 150 ml, after which the catheter was tied off at its lower end. The catheter was left in place for 24 hour or expelled with the fetus if the patient aborted earlier. If the abortion had not started by the following morning an intravenous infusion of oxytocin, 70 IU in 1000 ml of 5.5 % glucose, was commenced. This infusion was repeated every 12th hour until abortion occurred.
The indomethacin group were treated with 50 mg indomethacin (indomeem)orally every six hours for a maximum of seven doses with the first dose just before the instillation of Rivanol. A further instillation of Rivanol was performed if the patient had not aborted by 72 hours.
RESULTS The mean induction-abortion interval was 32.3 hours (range 13.0-96.0) in the control group and 46.9 hours (range 19.7-91.0) in the indomethacin group. The cumulative abortion rate for the control group versus the indomethacin-treated patients is shown in Fig. 1. All patients requiring a second instillation, aborted within a further 24 hours. Indornethacin significantly prolonged the induction-abortion interval ( p < 0 . 0 0 5 , Student's t-test). Excessive blood loss and endometritis were equally common in the two groups (control group: 10.9% and indomethacin group: 10%).
DISCUSSION Although Rivanol has been used to induce abortion for more than 20 years, the underlying mechanism is still obscure. An oxytoxic effect of related acridin dyes has been reported (2) but this does not fit in with the rather long initial lag time before the appearance of significant uterine contractions as reported by Martin et al. (3). Gustavii et al. (1) have shown endogenous release of prostaglandin after instillation of hypertonic saline for the induction of abortion. Waltman and collaborators (4) administered indomethacin, a strong inhibitor of prostaglandin synthesis, to patients undergoing
122
A . ii/und REFERENCES
%
'""1 501
,:-/;
A
- J/ 6
12
18
24
30
=indornethacin
.=control
36
,
,
,
,
,
42
48
54
60
66
, 72 hrs
Fig. 1. Percentage of patients aborting per six-hours unit of time.
saline-induced mid-trimester abortion. The result was a significantly prolonged instillation-abortion interval, supporting a prostaglandin mediated mechanism behind the abortifacient effect of hypertonic saline. Martin et al. (3) postulated a similar mechanism for Rivanol as for saline. The high incidence of gastrointestinal side effects with Rivanol (5) lends further support to this theory. The results of the present study, with a significant prolongation of the induction-abortion interval after the administration of indomethacin, strongly suggest that the effect of Rivanol is mediated through stimulation of the endogenous production of prostaglandins.
I. Gustavii, B. & GrCen, K.: Release of prostaglandin F,, following injection of hypertonic saline for therapeutic abortion: A preliminary study. Am J Obstet Gynecol 114: 1099, 1972. 2. Lewis, B . V., Pybus, A. & Stillwell, J. H.: The oxytocic effect of acndin dyes and their use in terminating mid-trimester pregnancy. J Obstet Gynaecol Br Comm 78: 838, 1971. 3. Martin, J. N., Bygdeman, M., Leader, A. & Wiqvist, N.: Early second trimester abortion by the extraamniotic instillation of Rivanol solution and a single PGF,, dose. Contraception 11: 523, 1975. 4. Waltman, R., Tricomi, V. & Palay, A,: Aspirin and indomethacin: Effect on instillation/abortion time of mid-trimester hypertonic saline induced abortion. Prostaglandins3: 47, 1973. 5 . Olund, A. R. & Larsson, B.: Comparision of extraamniotic instillation of Rivanol and PGF,, either separately or in combination followed by oxytocin for second trimester abortion. Acta Obstet Gynecol Scand 57: 333, 1978. Submitted for publieation Sepl. 8 , 1977
Anders Olund, M.D. Department of Obstetrics and Gynecology Huddinge Hospital S-14186 Huddinge Sweden
SHORT COMMUNICATION
THE EFFECT O F INDOMETHACIN ON THE INSTILLATIONABORTION INTERVAL IN RIVANOL-INDUCED MID-TRIMESTER ABORTION Anders Olund From the Department of Obstetrics and Gynecology, Karolinska instituter, Huddinge University Hospital, Huddinge, Sweden
Extra-amniotic instillation of Rivanol for the induction of mid-trimester abortion is a safe and effective method and its clinical value has been described in several reports (for ref. see (5)). The mechanism by which Rivanol induces abortion is, however, still obscure. It has been proposed that hypertonic saline induces abortion by stimulating the release of endogenous PGF2a (1). The fact that prostaglandin synthetase inhibitors prolong the inductionabortion interval in saline-induced abortion lends further support to this theory (4). The purpose of the present study was to examine possible effects of indomethacin, a strong prostaglandin synthetase inhibitor, on mid-trimester abortion induced by Rivanol.
MATERIAL AND METHODS Twenty women were included in the indomethacin group and 55 women in a control group who were admitted to the hospital for legal abortion during the period 1975-1977. The mean gestational age ( + I S.D.) was 16.1k2.7 weeks in the indomethacin group and 15.6f2.1 weeks in the control group. In all cases the abortion was induced by extra-amniotic instillation of Rivanol. A Foley balloon-catheter no. 20 was introduced into the extra-ovular space via the cervical canal. The tip of the catheter was placed just inside the internal 0s of the cervix and the balloon was filled with 30 ml of physiological saline. A 0.1 % solution of Rivanol was then slowly instilled, 10 ml per gestational week, but never more than 150 ml, after which the catheter was tied off at its lower end. The catheter was left in place for 24 hour or expelled with the fetus if the patient aborted earlier. If the abortion had not started by the following morning an intravenous infusion of oxytocin, 70 IU in 1000 ml of 5.5 % glucose, was commenced. This infusion was repeated every 12th hour until abortion occurred.
The indomethacin group were treated with 50 mg indomethacin (indomeem)orally every six hours for a maximum of seven doses with the first dose just before the instillation of Rivanol. A further instillation of Rivanol was performed if the patient had not aborted by 72 hours.
RESULTS The mean induction-abortion interval was 32.3 hours (range 13.0-96.0) in the control group and 46.9 hours (range 19.7-91.0) in the indomethacin group. The cumulative abortion rate for the control group versus the indomethacin-treated patients is shown in Fig. 1. All patients requiring a second instillation, aborted within a further 24 hours. Indornethacin significantly prolonged the induction-abortion interval ( p < 0 . 0 0 5 , Student's t-test). Excessive blood loss and endometritis were equally common in the two groups (control group: 10.9% and indomethacin group: 10%).
DISCUSSION Although Rivanol has been used to induce abortion for more than 20 years, the underlying mechanism is still obscure. An oxytoxic effect of related acridin dyes has been reported (2) but this does not fit in with the rather long initial lag time before the appearance of significant uterine contractions as reported by Martin et al. (3). Gustavii et al. (1) have shown endogenous release of prostaglandin after instillation of hypertonic saline for the induction of abortion. Waltman and collaborators (4) administered indomethacin, a strong inhibitor of prostaglandin synthesis, to patients undergoing
122
A . ii/und REFERENCES
%
'""1 501
,:-/;
A
- J/ 6
12
18
24
30
=indornethacin
.=control
36
,
,
,
,
,
42
48
54
60
66
, 72 hrs
Fig. 1. Percentage of patients aborting per six-hours unit of time.
saline-induced mid-trimester abortion. The result was a significantly prolonged instillation-abortion interval, supporting a prostaglandin mediated mechanism behind the abortifacient effect of hypertonic saline. Martin et al. (3) postulated a similar mechanism for Rivanol as for saline. The high incidence of gastrointestinal side effects with Rivanol (5) lends further support to this theory. The results of the present study, with a significant prolongation of the induction-abortion interval after the administration of indomethacin, strongly suggest that the effect of Rivanol is mediated through stimulation of the endogenous production of prostaglandins.
I. Gustavii, B. & GrCen, K.: Release of prostaglandin F,, following injection of hypertonic saline for therapeutic abortion: A preliminary study. Am J Obstet Gynecol 114: 1099, 1972. 2. Lewis, B . V., Pybus, A. & Stillwell, J. H.: The oxytocic effect of acndin dyes and their use in terminating mid-trimester pregnancy. J Obstet Gynaecol Br Comm 78: 838, 1971. 3. Martin, J. N., Bygdeman, M., Leader, A. & Wiqvist, N.: Early second trimester abortion by the extraamniotic instillation of Rivanol solution and a single PGF,, dose. Contraception 11: 523, 1975. 4. Waltman, R., Tricomi, V. & Palay, A,: Aspirin and indomethacin: Effect on instillation/abortion time of mid-trimester hypertonic saline induced abortion. Prostaglandins3: 47, 1973. 5 . Olund, A. R. & Larsson, B.: Comparision of extraamniotic instillation of Rivanol and PGF,, either separately or in combination followed by oxytocin for second trimester abortion. Acta Obstet Gynecol Scand 57: 333, 1978. Submitted for publieation Sepl. 8 , 1977
Anders Olund, M.D. Department of Obstetrics and Gynecology Huddinge Hospital S-14186 Huddinge Sweden
