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Intravenous prostaglandin F2α for therapeutic abortion
Intravenous
prostaglandin
F,, for therapeutic
abortion EDWARD
J.
KIRSHEN,
FREDERICK
NAFTOLIN,
KENNETH La Jolla
M.D.
J.
RYAN,
and San Diego,
M.D.,
PH.D.
M.D.
California
The use of prostaglandin Fta in increasing (25 to 250 mcg. per minute) and constant (50 to 100 mcg. per minute) doses via intravenous infusion in a grou# of 15 women undergoing therapeutic abortion is described. The constant lower dose regimen was superior to the graded dose Program from the standpoint of both obtaining abortion and minimizing side effects. Although no serious side effects were encountered, troublesome nausea, vomiting, and diarrhea were frequent. The occurrence of prolonged infusion times (which could not be forecast from the gestational age or parity of the patients), an over-all failure rate of 42 per cent, and the accompanying side eflects obviate this form of treatment as an alternative to suction evacuation of the uterus for routine theraleutic abortion.
s I N c E THE first publication of Karim and Filshiel on the use of prostaglandin F,CY in termination of early human pregnancy, many other authors2-T have described similar experiences with this compound. This report summarizes our experience with 15 patients in a preliminary study on the clinical use of prostaglandin F,CX to perform therapeutic abortion by the intravenous route. Material
and
cepted for this study (Table I). A complete history was obtained, and physical examination was performed on each patient to rule out any evidence of coexistent medical or gynecologic problems. Upon hospital admission, specimenswere obtained for a complete blood count, platelet count, complete urinalysis, serum chemistries (electrolytes, blood urea nitrogen, creatinine, serum glutamic oxalacetic transaminase, serum glutamic pyruvic transaminase, alkaline phosphatase, and bilirubin), blood glucose, serum progesterone, and plasma cortisol. These parameters were also studied during the maximally tolerated prostaglandin dose and on the first morning after treatment. On the morning of infusion, the patient underwent a careful pelvic examination to reassess uterine size, followed by the insertion of a 20 gauge epidural catheter* transcervitally into the myometrium. This catheter was connected to a tocodynamometer (FMS101 monitor+). After recording of base-line
methods
Fifteen patients, ages 17 to 32, parity 0 to 2, of 8 to 17 weeks’ gestation, with approval for therapeutic abortion, were acFrom the University of California, San Diego, School of Medicine, Department of Obstetrics and Gynecology, and University Hospital. This study grant from
was supported The Upjohn
in #art Company.
by a 25,
T;;;*ved
for publication
January
f;;;$ted
for publication
February
Reprint requests: Dept. of Ob./Gyn., 225 W. Dickinson California 92103.
14,
Dr.
E. 1. Kirshen, University Hospital, St., San Diego,
*Portex Ltd., Hythe Kent, England. +Corometrics Medical Systems, Inc., necticut.
340
New
Haven,
Con-
Volume Number
113 3
Intravenous
and intravital signs, electrocardiogram, uterine pressure, an infusion of prostaglandin F,a: at a concentration of 25 mcg. per milliliter was was begun via an indwelling intravenous catheter with an electrically driven infusion pump (Braun”) . The first 6 patients were treated in a stepwise manner over an increasing dose range of 25 to 250 mcg. per minute in a study designed to assess the proper dose range and therapeutic index for prostaglandin F2cz.+ As a result of this experience, the 9 most recently treated patients were given a constant infusion of 13.5 to 33 hours between 25 and 100 mcg. per minute (Table II). Vital signs and an electrocardiogram were obtained every half hour during the infusion and every 2 hours for the first 12 hours after the infusion.
Results Vital signs. Prior
to infusion all patients studied were afebrile (under 100° F.). The maximum temperature elevation during the infusion was to 100.8’ F.; no postinfusion elevations were noted. Only one patient exhibited a rise in blood pressure (114/60 to 140/90), and no instances of hypotension were observed. Pulse and respiratory rate did not vary significantly. Electrocardiogram. Tracings obtained throughout and after treatment failed to reveal any arrythmia, conduction defect, or irregularity. Hemogram. No patient exhibited a significant change in hemoglobin, white blood cell count, or platelet count during or after therapy; no patient required blood transfusion. Urinalysis. In no case was proteinuria, microscopic hematuria, or cast formation manifest during or after treatment. Blood chemistries. Renal and liver function tests were within normal limits throughout. Electrolytes also remained normal (except for potassium which was inaccurately determined because of improper serum storage). ‘Quigley-Rochester, tFurnished of The Upjohn
Inc.,
Rochester,
New
as the THAM salt by Dr. Co., Kalamazoo, Michigan.
PGF2a
for
therapeutic
abortion
Serum progesterone. No consistent effect upon serum progesterone during or after treatment was noted. Only 2 patients exhibited significantly decreased levels after prostaglandin infusion. Plasma cortisol. These values remained stable but with some suggestion of rise during the maximal dose. Uterine contractions. All patients achieved satisfactory uterine contractions after a period of from 15 minutes to 2 hours of infusion with either 50 or 100 mcg. per minute. All patients showed a rise in base-line tone from 10 to 50 mm. Hg during the course of therapy. Some achieved contractions of greater than 100 mm. Hg. Frequency and amplitude of contractions were usually, but not always, related. Side effects (Table I). No major complications were noted. Eleven patients had significant nausea with vomiting and/or diarrhea. Two additional patients had only minimal nausea. This was generally dose related but capricious in terms of time of appearance. Thus, side effects would appear suddenly in a patient who had been having an infusion dose that had not changed for two or more hours. Nausea and vomiting readily responded to small intramuscular doses of prochlorperazine.” Other complaints included transient flushing and local tissue reaction at the intravenous site in three patients. Abortion. Six patients aborted completely (i.e., complete expulsion of products of conception with no further surgical intervention) . Blood loss in these patients was estimated to be under 50 C.C. Three patients aborted incompletely (i.e., incomplete expulsion of products of conception) and required dilatation and curettage. Six patients failed to abort despite consistently strong uterine contractions and required dilatation and curettage. Comment Although 4 of 5 multigravid patients in this series aborted, there can be no definitive
York. E. M.
Southern
341
*Compazine, Pennsylvania.
Smith,
Kline
& French
Labs.,
Philadelphia,
342
Kirshen,
Naftolin,
and
June 1, 1972 J. Obstet. Cynecol.
Ryan .\m.
Table I. Summary
of 15 patients
treated
with
intravenous
prostaglandin
F,cr -__--.
Patient No.
Gravida/ Age 19 30 28 20 21 25 23 21 18 28 20 39 17 19 20
1 3’ 4 5 6 7 8 9 10 :: 13 14 15 *N
=
Nausea;
V
=
vomiting;
15 Normal
Weeks from last menstrual period
l/O 3/2 l/O l/O l/O l/O l/O l/O l/O 3/2 l/O 4/2 l/O 2/l 2/l
10 11 10 8 10 11 9 11 16 9 11 10 17 13 13
D
Table II. Dosage schedules prostaglandin
para
=
diarrhea;
FI
=
of intravenous
F,cu pregnant
Increasing dose steps (tolerance and eficacy study) of prostaglandin F$a (6 patients) 1. 25-250 mcg./min. over 12 hours 2. Rest 12 hours 3. Reinfuse, if needed
women
(8-I
7 weeks)
Constant dose step of prostaglandin F,ar (9 patients) 1. 50-100 mcg./min. over 24-33 hours. No reinfusion
assessment made of the effect of parity in the use of prostaglandin from these data. Similarly, the weeks of gestation ranged from 8 to 13 in the successful cases and from 8 to 17 in the unsuccessful cases, allowing no correlation to be made between duration of gestation and success of labor induction. The initial report of Karim and Filshiel revealed better success with pregnancies of 9 to 15 weeks’ gestation (100 per cent complete or partial abortion) as compared to those of 16 to 22 weeks’ gestation (83 per cent complete or partial abortion). Later data from Bygdeman and Wiqvist? support this finding with a 94 per cent complete or partial abortion result for less than 8 weeks and only a 20 to 30 per cent success rate between 9 and 16 weeks. In terms of toxicity, no major complica-
Dosage schedule Increasing Increasing Increasing Increasing Increasing Increasing Constant Constant Constant Constant Constant Constant Constant Constant Constant
flush;
LE
=
local
Outcome Failed Complete Complete Failed Incomplete Failed Incomplete Complete Failed Incomplete Complete Complete Failed Failed Comalete
abortion abortion abortion abortion abortion abortion abortion abortion
abortion
erythema.
tions were manifest either clinically or by laboratory assay. In our patients, the incidence of dysmenorrhea-like pain was 93 per cent at both 50 and 100 mcg. per minute. Bygdeman and Wiqvist7 report a 50 per cent rate at 50 mcg. per minute and 100 per cent at 100 mcg. per minute. Nausea, vomiting, and diarrhea were common minor side effects in our series (86 per cent at 50 mcg. per minute and 93 per cent at 100 mcg. per minute). Similar findings were reported by Karim and Filshiel and Bygdeman and Wiquist ;? especially with the higher doses used. In cases of complete abortion, blood loss was minimal (less than 50 c.c.) in comparison to abortion performed surgically (suction curettage) and medically (intra-amniotic instillation of saline or glucose) .8 The finding that all patients achieved good uterine contractions within 2 hours appears to be extremely important and is certainly consistent with earlier reports.2-5* g The pattern is one of early increase in uterine tone which is later replaced by rhythmic contractions of increased amplitude and decreased uterine tone. As in all other studies reported, each of our patients developed forceful uterine contractions during the treatment period. The effectiveness of prostaglandin F+Y in causing uterine contractions
Volume Number
113 3
Time to first contraction (min.)
15 60 45 15 50 30 15 45 30 120 120 20 120 120 45
Intravenous
Time to abortion (hr.)
18 11 14 31 13 25 26 6 f
Dilatation and curettage
After None None After None After Yes None After Yes None None Saline After None
12 + 3 hr. 12 + 6 hr. 24 + 12 hr. 23 hr.
injection 27 hr.
cannot be disputed. However, our over-all success rate (i.e., complete or partial abortion) of 60 per cent is lower than the 95 and 83 per cent reported by Karim and Filshiel and Bygdeman and Wiqvist,’ respectively. Our results did improve from a 50 to a 67 per cent success rate with the low dose, constant infusion regimen (50 to 10 mcg. per minute). In addition, the patients treated in this manner exhibited less of the troublesome side effects seen with the higher dose infusion. Regarding the treatment failures, the problem clearly appeared to be in the endocervix which did not dilate despite adequate uterine contractions. Kaufman and associates4 report a similar problem in their treatment failures. In our patients, there was effacement and dilatation of the external cervix with a hard, almost closed internal cervical OS that blocked the egress of the uterine contents which has been compacted down into the lower uterine segment. Thus, in some cases a so-called “failure to abort” will at least convert a patient normally requiring intrauterine saline or glucose infusion to one managed safely by dilatation and curettage. We have since seen a similar picture in the use of prostaglandin F,cr by the intravaginal and intrauterine route. In view of this experience, we feel that the use of intravenous infusion of prostaglandin
after 36 hr.
PGF2a for therapeutic
abortion
Highest dose (mcg./min.
Side effects*
250 250 250 250 250 250 100 100 100 100 100 50 100 100 50
)
343
N/V/D None V/D/FI/LE N/V/D N/V N/V/D N (Minimal) None N (Minimal) N/D N/V/LE N/V/D N/V/D N/V/F1 D
F,a! for termination of early human pregnancy is inferior to suction curettage in terms of efficacy and patient comfort and convenience. However, it may be of value in those pregnancies which currently require intraovular saline or hysterotomy. Recent reports lo* I1 do suggest that intravenous prostaglandin E, is more effective in terms of completion of abortion, infusion-abortion interval, and diminution of side effects. Currently, we are evaluating the use of other routes in the application of prostaglandin for abortion. In addition, we are beginning to explore adjuvant treatment to make the cervix more receptive to prostaglandin and thus overcome the most serious drawback to prostaglandin-induced therapeutic abortion. Addendum Since completion of this study, one additional patient was treated with intravenous prostaglandin F z~, A 19-year-old Caucasian woman, 16 weeks pregnant, was injected with 150 C.C.of hypertonic saline intra-amniotically. Because of no response by 72 hours, reinjection was attempted but was unsuccessful. Intravenous prostaglandin F,a, in progressively increasing doses (up to 80 mcg. per minute), resulted in strong uterine contractions as well as nausea and vomiting. There was no cervical dilatation, and abortion was effected by hysterotomy.
344
Kirshen, Naftolin,
June 1, 1972 Am. J. Ohstet. Cynecol.
and Ryan
REFERENCES
1. Karim,
S. M.
6. M.,
and
Filshie,
G. M.:
Lancet
1: 157, 1970. 2. 3.
4. 5.
Roth-Brandel, U., Bygdeman, M., Wiqvist, N., and Bergstrom, S.: Lancet 1: 190, 1970. Bygdeman, M., Kwon, S. U., Mukherjee, T., Roth-Brandel, U., and Wiqvist, N.: AM. J. OBSTET. GYNECOL. 106: 567, 1970. Kaufman, R. G., Freeman, R. K., and Mishell. D. R.: Contraceution 3: 121. 1971. Karim,’ S. M. M., HilIfer, K., Somers, K., and Trussell, R. R.: J. Obstet. Gynaecol. Br. Commonw. 78: 172, 1971.
7. 8. 9. 10. 11.
Hendricks, C. H., Brenner, W. E., Ekbladh, L., Brotanek, V., and Fishburne, J. I.: AM. .T. OBSTET. GYNECOL. 111: 564, 1971. Bygdeman, M., and Wiqvist, N.; Ann. N. I’. Acad. Sci. 180: 474. 1971. Brenner, P. H., K&hen, E. J., and Didio, J. M.: Calif. Med. 115: 20, 1971. Embrey, M. P.: J. Obstet. Gynaecol. Br. Commonw. 76: 783, 1969. Karim. S. M. M.. and Filshie. I G. M.: Br. Med. J. 3: 198, 1970. Embrey, M. P.: J. Reprod. Med. 6: 15, 1971.
prostaglandin
F,, for therapeutic
abortion EDWARD
J.
KIRSHEN,
FREDERICK
NAFTOLIN,
KENNETH La Jolla
M.D.
J.
RYAN,
and San Diego,
M.D.,
PH.D.
M.D.
California
The use of prostaglandin Fta in increasing (25 to 250 mcg. per minute) and constant (50 to 100 mcg. per minute) doses via intravenous infusion in a grou# of 15 women undergoing therapeutic abortion is described. The constant lower dose regimen was superior to the graded dose Program from the standpoint of both obtaining abortion and minimizing side effects. Although no serious side effects were encountered, troublesome nausea, vomiting, and diarrhea were frequent. The occurrence of prolonged infusion times (which could not be forecast from the gestational age or parity of the patients), an over-all failure rate of 42 per cent, and the accompanying side eflects obviate this form of treatment as an alternative to suction evacuation of the uterus for routine theraleutic abortion.
s I N c E THE first publication of Karim and Filshiel on the use of prostaglandin F,CY in termination of early human pregnancy, many other authors2-T have described similar experiences with this compound. This report summarizes our experience with 15 patients in a preliminary study on the clinical use of prostaglandin F,CX to perform therapeutic abortion by the intravenous route. Material
and
cepted for this study (Table I). A complete history was obtained, and physical examination was performed on each patient to rule out any evidence of coexistent medical or gynecologic problems. Upon hospital admission, specimenswere obtained for a complete blood count, platelet count, complete urinalysis, serum chemistries (electrolytes, blood urea nitrogen, creatinine, serum glutamic oxalacetic transaminase, serum glutamic pyruvic transaminase, alkaline phosphatase, and bilirubin), blood glucose, serum progesterone, and plasma cortisol. These parameters were also studied during the maximally tolerated prostaglandin dose and on the first morning after treatment. On the morning of infusion, the patient underwent a careful pelvic examination to reassess uterine size, followed by the insertion of a 20 gauge epidural catheter* transcervitally into the myometrium. This catheter was connected to a tocodynamometer (FMS101 monitor+). After recording of base-line
methods
Fifteen patients, ages 17 to 32, parity 0 to 2, of 8 to 17 weeks’ gestation, with approval for therapeutic abortion, were acFrom the University of California, San Diego, School of Medicine, Department of Obstetrics and Gynecology, and University Hospital. This study grant from
was supported The Upjohn
in #art Company.
by a 25,
T;;;*ved
for publication
January
f;;;$ted
for publication
February
Reprint requests: Dept. of Ob./Gyn., 225 W. Dickinson California 92103.
14,
Dr.
E. 1. Kirshen, University Hospital, St., San Diego,
*Portex Ltd., Hythe Kent, England. +Corometrics Medical Systems, Inc., necticut.
340
New
Haven,
Con-
Volume Number
113 3
Intravenous
and intravital signs, electrocardiogram, uterine pressure, an infusion of prostaglandin F,a: at a concentration of 25 mcg. per milliliter was was begun via an indwelling intravenous catheter with an electrically driven infusion pump (Braun”) . The first 6 patients were treated in a stepwise manner over an increasing dose range of 25 to 250 mcg. per minute in a study designed to assess the proper dose range and therapeutic index for prostaglandin F2cz.+ As a result of this experience, the 9 most recently treated patients were given a constant infusion of 13.5 to 33 hours between 25 and 100 mcg. per minute (Table II). Vital signs and an electrocardiogram were obtained every half hour during the infusion and every 2 hours for the first 12 hours after the infusion.
Results Vital signs. Prior
to infusion all patients studied were afebrile (under 100° F.). The maximum temperature elevation during the infusion was to 100.8’ F.; no postinfusion elevations were noted. Only one patient exhibited a rise in blood pressure (114/60 to 140/90), and no instances of hypotension were observed. Pulse and respiratory rate did not vary significantly. Electrocardiogram. Tracings obtained throughout and after treatment failed to reveal any arrythmia, conduction defect, or irregularity. Hemogram. No patient exhibited a significant change in hemoglobin, white blood cell count, or platelet count during or after therapy; no patient required blood transfusion. Urinalysis. In no case was proteinuria, microscopic hematuria, or cast formation manifest during or after treatment. Blood chemistries. Renal and liver function tests were within normal limits throughout. Electrolytes also remained normal (except for potassium which was inaccurately determined because of improper serum storage). ‘Quigley-Rochester, tFurnished of The Upjohn
Inc.,
Rochester,
New
as the THAM salt by Dr. Co., Kalamazoo, Michigan.
PGF2a
for
therapeutic
abortion
Serum progesterone. No consistent effect upon serum progesterone during or after treatment was noted. Only 2 patients exhibited significantly decreased levels after prostaglandin infusion. Plasma cortisol. These values remained stable but with some suggestion of rise during the maximal dose. Uterine contractions. All patients achieved satisfactory uterine contractions after a period of from 15 minutes to 2 hours of infusion with either 50 or 100 mcg. per minute. All patients showed a rise in base-line tone from 10 to 50 mm. Hg during the course of therapy. Some achieved contractions of greater than 100 mm. Hg. Frequency and amplitude of contractions were usually, but not always, related. Side effects (Table I). No major complications were noted. Eleven patients had significant nausea with vomiting and/or diarrhea. Two additional patients had only minimal nausea. This was generally dose related but capricious in terms of time of appearance. Thus, side effects would appear suddenly in a patient who had been having an infusion dose that had not changed for two or more hours. Nausea and vomiting readily responded to small intramuscular doses of prochlorperazine.” Other complaints included transient flushing and local tissue reaction at the intravenous site in three patients. Abortion. Six patients aborted completely (i.e., complete expulsion of products of conception with no further surgical intervention) . Blood loss in these patients was estimated to be under 50 C.C. Three patients aborted incompletely (i.e., incomplete expulsion of products of conception) and required dilatation and curettage. Six patients failed to abort despite consistently strong uterine contractions and required dilatation and curettage. Comment Although 4 of 5 multigravid patients in this series aborted, there can be no definitive
York. E. M.
Southern
341
*Compazine, Pennsylvania.
Smith,
Kline
& French
Labs.,
Philadelphia,
342
Kirshen,
Naftolin,
and
June 1, 1972 J. Obstet. Cynecol.
Ryan .\m.
Table I. Summary
of 15 patients
treated
with
intravenous
prostaglandin
F,cr -__--.
Patient No.
Gravida/ Age 19 30 28 20 21 25 23 21 18 28 20 39 17 19 20
1 3’ 4 5 6 7 8 9 10 :: 13 14 15 *N
=
Nausea;
V
=
vomiting;
15 Normal
Weeks from last menstrual period
l/O 3/2 l/O l/O l/O l/O l/O l/O l/O 3/2 l/O 4/2 l/O 2/l 2/l
10 11 10 8 10 11 9 11 16 9 11 10 17 13 13
D
Table II. Dosage schedules prostaglandin
para
=
diarrhea;
FI
=
of intravenous
F,cu pregnant
Increasing dose steps (tolerance and eficacy study) of prostaglandin F$a (6 patients) 1. 25-250 mcg./min. over 12 hours 2. Rest 12 hours 3. Reinfuse, if needed
women
(8-I
7 weeks)
Constant dose step of prostaglandin F,ar (9 patients) 1. 50-100 mcg./min. over 24-33 hours. No reinfusion
assessment made of the effect of parity in the use of prostaglandin from these data. Similarly, the weeks of gestation ranged from 8 to 13 in the successful cases and from 8 to 17 in the unsuccessful cases, allowing no correlation to be made between duration of gestation and success of labor induction. The initial report of Karim and Filshiel revealed better success with pregnancies of 9 to 15 weeks’ gestation (100 per cent complete or partial abortion) as compared to those of 16 to 22 weeks’ gestation (83 per cent complete or partial abortion). Later data from Bygdeman and Wiqvist? support this finding with a 94 per cent complete or partial abortion result for less than 8 weeks and only a 20 to 30 per cent success rate between 9 and 16 weeks. In terms of toxicity, no major complica-
Dosage schedule Increasing Increasing Increasing Increasing Increasing Increasing Constant Constant Constant Constant Constant Constant Constant Constant Constant
flush;
LE
=
local
Outcome Failed Complete Complete Failed Incomplete Failed Incomplete Complete Failed Incomplete Complete Complete Failed Failed Comalete
abortion abortion abortion abortion abortion abortion abortion abortion
abortion
erythema.
tions were manifest either clinically or by laboratory assay. In our patients, the incidence of dysmenorrhea-like pain was 93 per cent at both 50 and 100 mcg. per minute. Bygdeman and Wiqvist7 report a 50 per cent rate at 50 mcg. per minute and 100 per cent at 100 mcg. per minute. Nausea, vomiting, and diarrhea were common minor side effects in our series (86 per cent at 50 mcg. per minute and 93 per cent at 100 mcg. per minute). Similar findings were reported by Karim and Filshiel and Bygdeman and Wiquist ;? especially with the higher doses used. In cases of complete abortion, blood loss was minimal (less than 50 c.c.) in comparison to abortion performed surgically (suction curettage) and medically (intra-amniotic instillation of saline or glucose) .8 The finding that all patients achieved good uterine contractions within 2 hours appears to be extremely important and is certainly consistent with earlier reports.2-5* g The pattern is one of early increase in uterine tone which is later replaced by rhythmic contractions of increased amplitude and decreased uterine tone. As in all other studies reported, each of our patients developed forceful uterine contractions during the treatment period. The effectiveness of prostaglandin F+Y in causing uterine contractions
Volume Number
113 3
Time to first contraction (min.)
15 60 45 15 50 30 15 45 30 120 120 20 120 120 45
Intravenous
Time to abortion (hr.)
18 11 14 31 13 25 26 6 f
Dilatation and curettage
After None None After None After Yes None After Yes None None Saline After None
12 + 3 hr. 12 + 6 hr. 24 + 12 hr. 23 hr.
injection 27 hr.
cannot be disputed. However, our over-all success rate (i.e., complete or partial abortion) of 60 per cent is lower than the 95 and 83 per cent reported by Karim and Filshiel and Bygdeman and Wiqvist,’ respectively. Our results did improve from a 50 to a 67 per cent success rate with the low dose, constant infusion regimen (50 to 10 mcg. per minute). In addition, the patients treated in this manner exhibited less of the troublesome side effects seen with the higher dose infusion. Regarding the treatment failures, the problem clearly appeared to be in the endocervix which did not dilate despite adequate uterine contractions. Kaufman and associates4 report a similar problem in their treatment failures. In our patients, there was effacement and dilatation of the external cervix with a hard, almost closed internal cervical OS that blocked the egress of the uterine contents which has been compacted down into the lower uterine segment. Thus, in some cases a so-called “failure to abort” will at least convert a patient normally requiring intrauterine saline or glucose infusion to one managed safely by dilatation and curettage. We have since seen a similar picture in the use of prostaglandin F,cr by the intravaginal and intrauterine route. In view of this experience, we feel that the use of intravenous infusion of prostaglandin
after 36 hr.
PGF2a for therapeutic
abortion
Highest dose (mcg./min.
Side effects*
250 250 250 250 250 250 100 100 100 100 100 50 100 100 50
)
343
N/V/D None V/D/FI/LE N/V/D N/V N/V/D N (Minimal) None N (Minimal) N/D N/V/LE N/V/D N/V/D N/V/F1 D
F,a! for termination of early human pregnancy is inferior to suction curettage in terms of efficacy and patient comfort and convenience. However, it may be of value in those pregnancies which currently require intraovular saline or hysterotomy. Recent reports lo* I1 do suggest that intravenous prostaglandin E, is more effective in terms of completion of abortion, infusion-abortion interval, and diminution of side effects. Currently, we are evaluating the use of other routes in the application of prostaglandin for abortion. In addition, we are beginning to explore adjuvant treatment to make the cervix more receptive to prostaglandin and thus overcome the most serious drawback to prostaglandin-induced therapeutic abortion. Addendum Since completion of this study, one additional patient was treated with intravenous prostaglandin F z~, A 19-year-old Caucasian woman, 16 weeks pregnant, was injected with 150 C.C.of hypertonic saline intra-amniotically. Because of no response by 72 hours, reinjection was attempted but was unsuccessful. Intravenous prostaglandin F,a, in progressively increasing doses (up to 80 mcg. per minute), resulted in strong uterine contractions as well as nausea and vomiting. There was no cervical dilatation, and abortion was effected by hysterotomy.
344
Kirshen, Naftolin,
June 1, 1972 Am. J. Ohstet. Cynecol.
and Ryan
REFERENCES
1. Karim,
S. M.
6. M.,
and
Filshie,
G. M.:
Lancet
1: 157, 1970. 2. 3.
4. 5.
Roth-Brandel, U., Bygdeman, M., Wiqvist, N., and Bergstrom, S.: Lancet 1: 190, 1970. Bygdeman, M., Kwon, S. U., Mukherjee, T., Roth-Brandel, U., and Wiqvist, N.: AM. J. OBSTET. GYNECOL. 106: 567, 1970. Kaufman, R. G., Freeman, R. K., and Mishell. D. R.: Contraceution 3: 121. 1971. Karim,’ S. M. M., HilIfer, K., Somers, K., and Trussell, R. R.: J. Obstet. Gynaecol. Br. Commonw. 78: 172, 1971.
7. 8. 9. 10. 11.
Hendricks, C. H., Brenner, W. E., Ekbladh, L., Brotanek, V., and Fishburne, J. I.: AM. .T. OBSTET. GYNECOL. 111: 564, 1971. Bygdeman, M., and Wiqvist, N.; Ann. N. I’. Acad. Sci. 180: 474. 1971. Brenner, P. H., K&hen, E. J., and Didio, J. M.: Calif. Med. 115: 20, 1971. Embrey, M. P.: J. Obstet. Gynaecol. Br. Commonw. 76: 783, 1969. Karim. S. M. M.. and Filshie. I G. M.: Br. Med. J. 3: 198, 1970. Embrey, M. P.: J. Reprod. Med. 6: 15, 1971.