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Use of combination prostaglandin F2α and hypertonic saline for midtrimester abortion
PROSTAGLANDINS
USE OF COMBINATION PROSTAGLANDIN FYAND HYPERTONIC SALINE FOR MIDTRIMESTER ABORTION MAX BORTEN, M.D. From the Department of Obstetrics and Gynecology Harvard Medical School, Beth Israel Hospital, Boston, Massachusetts Abstract Midtrimester abortion was induced by intraamniotic prostaglandin Fw in combination with hypertonic saline in 102 patients and by hypertonic saline alone in 102 others. Abortion time and duration of hospital stay were shorter with the prostaglandinsaline combination.
OCTOBER
1976
VOL. 12 NO. 4
625
PROSTAGLANDINS
Recent publications (1,2,3,4) have shown that the intraamniotic administration of prostaglandin F2y (PGF2a is effective for inducing abortion in second trimester pregnancies. The intraamniotic route succeeded in circumventing some of the systemic side effects which precluded the clinical application of this drug by the intravenous route (5,6,7). However, negative attributes of a single drug instillation included a high incidence of retained placental tissue after fetal expulsion and the delivery of live, albeit nonviable fetuses. The possibility of combining PGFZYwith just enough hypertonic saline solution was suggested for purposes of overcoming these problems while averting those serious complications occurring with the use of hypertonic saline alone (8,9,10). Accordingly, a series of midtrimester abortions was undertaken using a combination of PGFZI
626
OCTOBER
1976
VOL. 12 NO. 4
PROSTAGLANDINS
In addition the time intervals from injection to the passage of the fetus and the delivery of the placenta were calculated. Side effects (nausea, vomiting, diarrhea and pruritus) and complications (fever of more than 38oC, hemorrhage considered when a fall in the hematocrit was greater than 3 points, etc.) were all carefully detailed. Results Abortifacient Efficacy Of the 102 patients who were given the PGF2o4-salinecombination, 101 (99%) aborted within 72 hours; This compared favorably with the success rate among those receiving hypertonic saline only (96 in 102 or 94.1%), but the difference was only of borderline significance statistically (p=O.OS); Although,(as it is shown in fig. 1) after 48 hours following the instillation of the drugs, 99 of the 102 patients (97%) who were given the PGF2 -saline combination had succesfully aborted compared with only 82 of the 102 patients or (80%) who received hypertonic saline alone. The overall average instillation-to-abortion time in the combined agent group was 18.8 zl.0 hr. as contrasted with 34.021.3 hr. for hypertonic saline alone (p(O.001). Abortion was complete (fetus and placenta passed without need of instrumental aid) in 74 (72.6%) in the study group and 89 (87.3%) in the saline series (p=O.Ol). Instrumental procedures were used to effect completion in the remaining patients in both groups. The mean instillation-to-placeyta duration was 21.921.1 hr. in those receiving PGF24ksaline and 35.5-1.4 hr. in the saline aborions (p 0.0011. The fetus-to-placenta time averaged 3.1zO.4 hr. and 1.520.5 hr. respectively (p=O.O3). These differences were mirrored in each stratified gestational age duration subgroup that was studied (Table I)
Time from Injection to Abortion, hr.
OCTOBER 1976
VOL. 12 NO. 4
627
PROSTAGLANDINS
Fig. 1: Effectiveness of PGF2a(-salinecombination, administered intraamniotically in succesfully inducing midtrimester abortion, as compared with 20% hypertonic saline given alone, for total series (heavy solid line) and for gestational subgroups: 16-17 weeks (thin broken line), 18 weeks (dotted line), 19-20 weeks (thin solid line). Adverse Effects Among the side effects encountered (Table II), nausea, vomiting and diarrhea were predominant in the prostaglandin-saline group. By contrast, patients who received intraamniotic hypertonic saline developed morbidity (fever, cervical laceration) more often. One of the latter required readmission for curretage because of continued bleeding due to retained placental tissue. In the course of this study no coagulopathy was encountered in either group. There were no liveborn fetuses. Table II: Incidence of adverse effects of abortifacient agents Saline
PGFZI(+ saline Nausea Vomiting Nausea and Vomiting Diarrhea Pruritus Hemorrhage Fever Cervical laceration
14 7 10 5 1 7 4
5
6 9 1
Conclusion This comparative study illustrates that the intraamniotic instillation of the combination of 40 mg. of prostaglandin F20(and 50 ml of 20% hypertonic saline can effectively produce abortion in the second trimester pregnancy ( 16 to 20 weeks). It appears to offer advantages over the injection of 20% hypertonic saline solution alone. It reduces the time from instillation to evacuation almost in half. Countering this, however, is the unexpectedly high frequency of retained placenta, requiring instrumental or manual intervention. This is reflected in the elongation of the interval from delivery of the fetus to the passage of the placenta. Despite this, the duration from instillation to complete uterine emptying was foreshortened by 38% overall (43% in the 16-17 week gestational age group). Furthermore, no live births occurred. The mean time from instillation to abortion of the fetus in the prostaglandin-saline combination group showed no significant difference when compared to groups of patients aborted by intraamniotic PGF2 alone (11,12). Patient acceptance of the prostaglandin-saline combination regimen was enhanced by the reduction of the cost of the procedure. Although not specifically studied, a general impression prevailed that the reduction in instillation-to-abortion time was also associated with a concomitant reduction in anxiety and depression.
628
OCTOBER
1976
VOL. 12 NO. 4
PROSTAGLANDINS
REFERENCES 1.
2. 3. 4. 5. 6. 7. 8. 9. 10.
11. 12.
Anderson G.G.,Hobbins V.,Rajkovic V.,Speroff L. and Caldwell B.V.: Midtrimester abortion using intraamniotic prostaglandin F&(. Prostaglandin 1: 147, 1972 Bygdeman M.,Toppozada M. and Wiqvist N.: Induction of midtrimester abortion by intraamniotic administration of prostaglandin F;#. Acta Physiol. Stand. 81: 415, 1971 Karim S.M.M. and Sharma S.D.: Second trimester abortion with single intraamniotic iniection of orostaalandin E2 or FW. m. Lancet 2: 47, 19?1 Toppozada M.,Bygdeman M. and Wiqvist N.: Induction of abortion by intraamniotic administration of prostaglandin F2& Contraception 4: 293, 1971 Gillet P.G.,Kinch R.A.H.,Wolfe L.S. and Pace-Asciak C.: Therapeutic abortion with the use of prostaglandin F28(. Amer. J. Obstet. Gynec. 112: 330, 1972 Karim S.M.M. and Filshie G.M.: Therapeutic abortion using prostaglandin Fao(.Lancet 1: 157, 1970 . . Wiqvist N.,Bygdeman M. and Toppozada M.: Induction of abortion by the intravenous administration of prostaglandin Fw A critical evaluation. Acta Obstet. Gynec. 50: 381, 1971 Beller F.K.,Rosemberg M.Kolker R.M. and Douglas G.W.: Comsumptive coagulopathy associated with the intraamniotic infusion of hypertonic salt. Amer. J. Obstet. Gynec. 112: 534, 1972 Gordon R.T.: Cervicovaginal fistula as a result of saline abortion. Amer. J. Obstet. Gynec. 112: 578, 1972 Sedagamat A. and Ayromlooi J.: Disseminated intravascular coagulation resulting in severe hemorrhage following the intraamniotic injection of hypertonic saline to induce abortion. Amer. J. Obstet. Gynec. 114: 841, 1972 Lauersen N.H. and Wilson K.H.: Midtrimester abortion induced with a single intraamniotic instillation of prostaglandin F20(. Amer. J. Obstet. Gynec. 118: 210, 1974 Golbus M.S.: Laminaria and intraamniotic prostaglandin F2qfor induction of midtrimester abortions. Amer. J. Obstet. Gynec. 119: 569, 1974
OCTOBER
1976
VOL. 12 NO. 4
629
36 36
42 42
24 24
16 + 17 weeks PGFZO(+ saline Saline
18 weeks PGFN+ saline Saline
19 + 20 weeks PGFH + saline Saline 75.0 87.5
76.2 88.1
66.7 86.1
72.5 87.3
Complete
of intraamniotic
25.0 8.3
21.4 7.1
33.3 5.6
26.4 6.9
0.0 4.2
2.4 4.8
0.0 8.3
1.0 5.9
Success rate, % Incomplete Failure
efficacy
versus
saline alone
18.9+1.9t 32.2r2.6
19.4+1.5f 32.221.7
18.0+1.9t 37.622.5
2.3kO.6 l.Of0.5
2.320.4 1.420.6
4.6fl.l 2.2t1.2
3.120.4 1.520.5
21.2*2.0t 33.2i2.7
21.7+1.6-t33.621.8
22.6f2.4f 39.8+3-l
21.9,+1.1t 35.521.4
Time to abortion * Placenta Total
18.8kl.Oi 34.021.3
Fetus
PGFW-saline
* Duration in hours 2 standard error from instillation of abortifacient to expulsion of fetus, from expulsion of fetus to delivery of the placenta and from instillation of the abortifacient to the delivery of the placenta. tstatistically significant difference, p 0.01 by t-test.
102 102
TOTAL SERIES PGFZti + saline Saline
No.
Table I. Data on abortifacient
USE OF COMBINATION PROSTAGLANDIN FYAND HYPERTONIC SALINE FOR MIDTRIMESTER ABORTION MAX BORTEN, M.D. From the Department of Obstetrics and Gynecology Harvard Medical School, Beth Israel Hospital, Boston, Massachusetts Abstract Midtrimester abortion was induced by intraamniotic prostaglandin Fw in combination with hypertonic saline in 102 patients and by hypertonic saline alone in 102 others. Abortion time and duration of hospital stay were shorter with the prostaglandinsaline combination.
OCTOBER
1976
VOL. 12 NO. 4
625
PROSTAGLANDINS
Recent publications (1,2,3,4) have shown that the intraamniotic administration of prostaglandin F2y (PGF2a is effective for inducing abortion in second trimester pregnancies. The intraamniotic route succeeded in circumventing some of the systemic side effects which precluded the clinical application of this drug by the intravenous route (5,6,7). However, negative attributes of a single drug instillation included a high incidence of retained placental tissue after fetal expulsion and the delivery of live, albeit nonviable fetuses. The possibility of combining PGFZYwith just enough hypertonic saline solution was suggested for purposes of overcoming these problems while averting those serious complications occurring with the use of hypertonic saline alone (8,9,10). Accordingly, a series of midtrimester abortions was undertaken using a combination of PGFZI
626
OCTOBER
1976
VOL. 12 NO. 4
PROSTAGLANDINS
In addition the time intervals from injection to the passage of the fetus and the delivery of the placenta were calculated. Side effects (nausea, vomiting, diarrhea and pruritus) and complications (fever of more than 38oC, hemorrhage considered when a fall in the hematocrit was greater than 3 points, etc.) were all carefully detailed. Results Abortifacient Efficacy Of the 102 patients who were given the PGF2o4-salinecombination, 101 (99%) aborted within 72 hours; This compared favorably with the success rate among those receiving hypertonic saline only (96 in 102 or 94.1%), but the difference was only of borderline significance statistically (p=O.OS); Although,(as it is shown in fig. 1) after 48 hours following the instillation of the drugs, 99 of the 102 patients (97%) who were given the PGF2 -saline combination had succesfully aborted compared with only 82 of the 102 patients or (80%) who received hypertonic saline alone. The overall average instillation-to-abortion time in the combined agent group was 18.8 zl.0 hr. as contrasted with 34.021.3 hr. for hypertonic saline alone (p(O.001). Abortion was complete (fetus and placenta passed without need of instrumental aid) in 74 (72.6%) in the study group and 89 (87.3%) in the saline series (p=O.Ol). Instrumental procedures were used to effect completion in the remaining patients in both groups. The mean instillation-to-placeyta duration was 21.921.1 hr. in those receiving PGF24ksaline and 35.5-1.4 hr. in the saline aborions (p 0.0011. The fetus-to-placenta time averaged 3.1zO.4 hr. and 1.520.5 hr. respectively (p=O.O3). These differences were mirrored in each stratified gestational age duration subgroup that was studied (Table I)
Time from Injection to Abortion, hr.
OCTOBER 1976
VOL. 12 NO. 4
627
PROSTAGLANDINS
Fig. 1: Effectiveness of PGF2a(-salinecombination, administered intraamniotically in succesfully inducing midtrimester abortion, as compared with 20% hypertonic saline given alone, for total series (heavy solid line) and for gestational subgroups: 16-17 weeks (thin broken line), 18 weeks (dotted line), 19-20 weeks (thin solid line). Adverse Effects Among the side effects encountered (Table II), nausea, vomiting and diarrhea were predominant in the prostaglandin-saline group. By contrast, patients who received intraamniotic hypertonic saline developed morbidity (fever, cervical laceration) more often. One of the latter required readmission for curretage because of continued bleeding due to retained placental tissue. In the course of this study no coagulopathy was encountered in either group. There were no liveborn fetuses. Table II: Incidence of adverse effects of abortifacient agents Saline
PGFZI(+ saline Nausea Vomiting Nausea and Vomiting Diarrhea Pruritus Hemorrhage Fever Cervical laceration
14 7 10 5 1 7 4
5
6 9 1
Conclusion This comparative study illustrates that the intraamniotic instillation of the combination of 40 mg. of prostaglandin F20(and 50 ml of 20% hypertonic saline can effectively produce abortion in the second trimester pregnancy ( 16 to 20 weeks). It appears to offer advantages over the injection of 20% hypertonic saline solution alone. It reduces the time from instillation to evacuation almost in half. Countering this, however, is the unexpectedly high frequency of retained placenta, requiring instrumental or manual intervention. This is reflected in the elongation of the interval from delivery of the fetus to the passage of the placenta. Despite this, the duration from instillation to complete uterine emptying was foreshortened by 38% overall (43% in the 16-17 week gestational age group). Furthermore, no live births occurred. The mean time from instillation to abortion of the fetus in the prostaglandin-saline combination group showed no significant difference when compared to groups of patients aborted by intraamniotic PGF2 alone (11,12). Patient acceptance of the prostaglandin-saline combination regimen was enhanced by the reduction of the cost of the procedure. Although not specifically studied, a general impression prevailed that the reduction in instillation-to-abortion time was also associated with a concomitant reduction in anxiety and depression.
628
OCTOBER
1976
VOL. 12 NO. 4
PROSTAGLANDINS
REFERENCES 1.
2. 3. 4. 5. 6. 7. 8. 9. 10.
11. 12.
Anderson G.G.,Hobbins V.,Rajkovic V.,Speroff L. and Caldwell B.V.: Midtrimester abortion using intraamniotic prostaglandin F&(. Prostaglandin 1: 147, 1972 Bygdeman M.,Toppozada M. and Wiqvist N.: Induction of midtrimester abortion by intraamniotic administration of prostaglandin F;#. Acta Physiol. Stand. 81: 415, 1971 Karim S.M.M. and Sharma S.D.: Second trimester abortion with single intraamniotic iniection of orostaalandin E2 or FW. m. Lancet 2: 47, 19?1 Toppozada M.,Bygdeman M. and Wiqvist N.: Induction of abortion by intraamniotic administration of prostaglandin F2& Contraception 4: 293, 1971 Gillet P.G.,Kinch R.A.H.,Wolfe L.S. and Pace-Asciak C.: Therapeutic abortion with the use of prostaglandin F28(. Amer. J. Obstet. Gynec. 112: 330, 1972 Karim S.M.M. and Filshie G.M.: Therapeutic abortion using prostaglandin Fao(.Lancet 1: 157, 1970 . . Wiqvist N.,Bygdeman M. and Toppozada M.: Induction of abortion by the intravenous administration of prostaglandin Fw A critical evaluation. Acta Obstet. Gynec. 50: 381, 1971 Beller F.K.,Rosemberg M.Kolker R.M. and Douglas G.W.: Comsumptive coagulopathy associated with the intraamniotic infusion of hypertonic salt. Amer. J. Obstet. Gynec. 112: 534, 1972 Gordon R.T.: Cervicovaginal fistula as a result of saline abortion. Amer. J. Obstet. Gynec. 112: 578, 1972 Sedagamat A. and Ayromlooi J.: Disseminated intravascular coagulation resulting in severe hemorrhage following the intraamniotic injection of hypertonic saline to induce abortion. Amer. J. Obstet. Gynec. 114: 841, 1972 Lauersen N.H. and Wilson K.H.: Midtrimester abortion induced with a single intraamniotic instillation of prostaglandin F20(. Amer. J. Obstet. Gynec. 118: 210, 1974 Golbus M.S.: Laminaria and intraamniotic prostaglandin F2qfor induction of midtrimester abortions. Amer. J. Obstet. Gynec. 119: 569, 1974
OCTOBER
1976
VOL. 12 NO. 4
629
36 36
42 42
24 24
16 + 17 weeks PGFZO(+ saline Saline
18 weeks PGFN+ saline Saline
19 + 20 weeks PGFH + saline Saline 75.0 87.5
76.2 88.1
66.7 86.1
72.5 87.3
Complete
of intraamniotic
25.0 8.3
21.4 7.1
33.3 5.6
26.4 6.9
0.0 4.2
2.4 4.8
0.0 8.3
1.0 5.9
Success rate, % Incomplete Failure
efficacy
versus
saline alone
18.9+1.9t 32.2r2.6
19.4+1.5f 32.221.7
18.0+1.9t 37.622.5
2.3kO.6 l.Of0.5
2.320.4 1.420.6
4.6fl.l 2.2t1.2
3.120.4 1.520.5
21.2*2.0t 33.2i2.7
21.7+1.6-t33.621.8
22.6f2.4f 39.8+3-l
21.9,+1.1t 35.521.4
Time to abortion * Placenta Total
18.8kl.Oi 34.021.3
Fetus
PGFW-saline
* Duration in hours 2 standard error from instillation of abortifacient to expulsion of fetus, from expulsion of fetus to delivery of the placenta and from instillation of the abortifacient to the delivery of the placenta. tstatistically significant difference, p 0.01 by t-test.
102 102
TOTAL SERIES PGFZti + saline Saline
No.
Table I. Data on abortifacient