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A Preliminary Report on the Clinical Use of Methergine
A PRELIMINARY REPORT ON THE CLINICAL USE OF METHERGINE BENJAMIN
L.
GrPSTEIN,
1\i.D.,
SPRINGFIELD, MASS.
T
HE intravenous use of oxytocic drugs has proved of great value in preventing and reducing obstetric hemorrhage. The present study was therefore undertaken in order to determine the effectiveness of Methergine, a synthetic ergonovine derivative. This substance was partially synthesized by Stoll and Hofmann. and subsequently studied pharmacologically by Kirchhof and his associates. Previous clinical studies by Tollefson, Cartwright, and Rogers, Roberts, Hepp, and Evans, and Tritsch and Schneider have demonstrated Methergine to be a potent oxytocic as regards reduction of blood loss, shortening of the third stage of labor, and promotion of involution. l\fy objective in using this new synthetic drug, Methergine, was to observe its action on the postpartum uterus; the duration of the third stage; the amount of blood loss; postpartum pain; the character and amount of lochia; and finally to compare the amount of the drug necessary to obtain the same results as have been obtained with other oxytocics.
Procedure In all of the 180 cases in this series, a 1 c.c. ampule of Methergine, containing 0.2 mg. of the drug, was given intravenously immediately after the birth of the child, and another 1 c.c. was given intramuscularly as soon as the placenta was delivered. Pollowing the first intravenous injection, the uterus was massaged in order to attempt the expression of the placenta with the first hard contraction. This technique of manual expression, in my opinion, minimizes the blood loss and also the inddence of incarcerated placenta. Following delivery, the first Methergine tablet (0.25 mg.) was given orally in about four to six: hours, and repeated three times daily for two days unless more was thought necessary due to excessive bleeding. The latter was the exception rather than the rule. From the birth of the child to the time when the patient was taken down from the stirrups, all the blood lost vaginally, including that from the episiotomy, was collected in a sterile basin, held below the buttocks, and measured. Duration of the Third Stage A short third stage was characteristic of this series. As a rule, the first contraction after the intravenous use of Methergine was exceptionally forceful. After expression of the placenta, the uterus became very hard and round, maintained this tone for several hours, and could be palpated more often in the midline than to one side. By the time the patient's legs were off the stirrups, there was usually only a slight trickle of blood from the vagina and, i£ the fundus of the uterus was held abdominally between the palms of both hands for fifteen to twenty minutes, this status quo lasted until the action of Methergine had worn off hours later. The shortest third stage was one minute, with one exception, when the placenta was expressed with a stillborn fetus. The longest duration was fortyone minutes, giving a mean average of four and one-half minutes. The average length of the third stage in primiparas was 3.2 minutes, and in multiparas 4.6 minutes. 1065
Am. j. Ol,t, & Gyne,·.
GIPS'rEIN
1066
December, 194 7
The length of the third stage in 157 cases ( 87.2 per eent) was np to five minutes. In 18 cases (10.0 per cent), it was between six to fifteen minutes, and in five cases (2.8 per cent) it was between sixteen to forty-one minutes. TABLE I
I'El!CENTMIE
CASES
157
0 to ::i (i to 13
18 5
87.2 10.0
16 to 41 ---
Blood Loss in Third Stage It is interesting to note that one-half of this series fell into the group where the blood loss ranged between 50 to 100.
60 to lOll 101 to 449 450 and over
40 17 ()
II
:i4.K
:.J:U 0.0
GO
10 7
46.8 9.3 6.5 100.0
A brief review of three cases who lost more than 50 c.c. and less than 450 c.c. is presented: CASE No. 2l.~R. A., aged 26 years, pata i. Pressure on admission 200/100, postpartum 76/66. Bclampsia with abruptio. Outlet forceps and episiotomy. Morbidity 99.2 to 100.0. Postpartum shock. Uterus five fingers above symphysis immediately post partum, and one fingerbreadth above symphysis on discharge. Placenta delivered with stillborn. Scant serous lochia throughout. No abdominal pain throughout. Measured blood loss third stage 200 c.c. The complicating toxemia and premature detachment of the placenta were, no doubt, responsible for the greater blood loss. CASE No. 64.~-C. B., aged 24 years, para i. Midforceps and episiotomy. Pressure on admission 100/62, after delivery 98/68. Placenta expressed after thirty-five minutes incarceration by cervix (removal spontaneous). No morbidity. Uterus six fingers above symphysis after delivery, and two fingers above on discharge. Slight pain (cramps) first day. Spotting after third day. Measured blood loss 200 c.c., probably a result of retained placenta. CASE No. 82.-S. S., aged 34 years, para viii. Spontaneous delivery. Blood pressure on admission 130/92, after delivery 110/70. Retained, adherent placenta with manual removal. Uterus six fingers above symphysis after delivery, and two and one-half fingers on discharge. No morbidity. Spotting after third day. Slight cramps during first two days. Measured blood loss 100 c.c.
Volume 54 Number 6
CLINICAL USE OF MJ;;THERGINE
1067
Blood Loss Over 450 Cubic Centimeters CAsE No. 4.-A. S., aged 31 years, para ii. Outlet forceps and episiotomy. Blood pressure 124/60 to 118/64. Membranes ruptured mechanically when fully dilated. Uterus atonic after five minutes at the end of the third stage, and second ampule of Methergine was given intramuscularly, followed by firm contraction with massage. No morbidity. Slight cramps on first day. Placenta delivered in three minutes. No flow on tenth day. Uterus six fingers above symphysis after delivery, and three fingers above on discharge. Blood loss 500 c.c. The reason for this amount of bleeding is obscure. CASE No. 15.-A. M., aged 2fi years, para iv. Blood pressure 112/78 to 120/82. Outlet forceps, no episiotomy. Gush of blood with birth of head. Several clots after expression of placenta in two minutes, and second ampule of Methergine was given intramuscularly. No morbidity. Uterus six fingers above symphysis after delivery and one and one-half fingers above on discharge. Cramps on first day. Scant spotting on tenth day. Blood loss measured 500 cubic centimeters. CASE No. 59.-J. R., aged 24 years, para ii (Dr. M.F.G.). Outlet forceps, left episiotomy. Blood pressure 122/78. Placenta expressed in three minutes. No morbidity. No cramps. Very slight flow on discharge. Measured blood loss 500 c.c. probably due to bleeding vessel in episiotomy. CASE No. 62.-E. M. L., aged 32 years, para iii (Dr. M.F.G.). Spontaneous delivery. Placenta expressed in four minutes. Two ampules Methergine given intravenously. Slight cramps first two days. No morbidity. No flow after third day. Uterus six fingers above symphysis after delivery, and three above on discharge. Measured blood loss 800 c.c., due in part to laceration through scar tissue.
Postpartum Pain and Lochia About one-half the patients, more especially the multiparas, complained of slight cramps on the first postpartum day. These cramps started about fifteen to twenty minutes after receiving their first Methergine tablet, and lasted from one-half to two hours. No one eomplained of afterpains after the seeond day. Generally, postpartum pain was much less, and the uterus was less tender than when other oxytocies were used. Each day the size of the contracted uterus could be felt at a lower level, so that by the eighth postpartum day it could be palpated at between one to two finger breadths above the symphysis. To date, there have been no postpartum hemorrhages in this series, nor has any woman had a ''gush of blood'' oJt getting out of bed. Eleven cases, or 5 per cent, had an elevation of temperature of 99.4° F. or more for two consecutive days. These could be further corre-cted if we take into consideration that elevation in temperature was connected with full and engorged breasts. Except for occasional irregular spotting after leaving the hospital, most patients had a thin lochia, after the third or fourth day post partum, devoid of a foul odor. By the time of their six-week check-up the uterus was completely involuted. There was less complaint of low backache; the red cell count showed no more than a mild hypochromic anemia; and their general physical condition was good. Summary A series of 180 cases are presented in which a new synthetic drug, .Ylethergine, was used. The third stage of labor was appreciably shortened. The blood loss in the third stage was decreased.
lOGS
GIPSTEIN
Am.]. Ob,t. & Gynec. December, 1947
The prolonged action of the drug required less medication post partum. Postpartum bleeding and the umount of the lochia was decreased. Irwolution took place sooner· and the general condition of the patient was enhanced by its judicious nsc.
Conclusion 1\fethergine is a new synthetic oxytocic which seems to be very effective and safe when used in the third stage of labor. I wish to express my thanks to Bandoz Chemical Works, Inc., who supplied both the ampules and tablets o:f Methergine used in this eeries. To the Sisters of Providence and the nurses at the Mercy Hospital, and to Dr. Milton F. Gipstein, I express my gratitude for their cooperation and help in r~olleding r1ata.
References Cartwright, E. W., and Rogers, W. C.: West. J. Surg. 54: 59, 1946. Bepp. L. C., and Evans, J. R.: Rocky Mountain M . .J. 42: 949, 1945. Kirchhof, A. C., Racely, C. A .. Wilson, W. M., and David, N. A.: West. J. Surg. 52: 197, 1944. Kirchhof, A. C., Phatak, N. M., and Racely, C. A.: Federation Proceedings 3: 76, 1944. Robert~, P. C.: West. J. Surg. 52: 380, 1944. 'Stoll, A., and Hofmann, A.: Helvetica Chimica Acta 26; 944, 194:3. TollefRon, D. G.: West. J. Surg. 52: 383, 1944. Tritsch, J. E., and Schneider, E.: AM. ,T. OBST. & GYNEC. 50: 434, 1945.
L.
GrPSTEIN,
1\i.D.,
SPRINGFIELD, MASS.
T
HE intravenous use of oxytocic drugs has proved of great value in preventing and reducing obstetric hemorrhage. The present study was therefore undertaken in order to determine the effectiveness of Methergine, a synthetic ergonovine derivative. This substance was partially synthesized by Stoll and Hofmann. and subsequently studied pharmacologically by Kirchhof and his associates. Previous clinical studies by Tollefson, Cartwright, and Rogers, Roberts, Hepp, and Evans, and Tritsch and Schneider have demonstrated Methergine to be a potent oxytocic as regards reduction of blood loss, shortening of the third stage of labor, and promotion of involution. l\fy objective in using this new synthetic drug, Methergine, was to observe its action on the postpartum uterus; the duration of the third stage; the amount of blood loss; postpartum pain; the character and amount of lochia; and finally to compare the amount of the drug necessary to obtain the same results as have been obtained with other oxytocics.
Procedure In all of the 180 cases in this series, a 1 c.c. ampule of Methergine, containing 0.2 mg. of the drug, was given intravenously immediately after the birth of the child, and another 1 c.c. was given intramuscularly as soon as the placenta was delivered. Pollowing the first intravenous injection, the uterus was massaged in order to attempt the expression of the placenta with the first hard contraction. This technique of manual expression, in my opinion, minimizes the blood loss and also the inddence of incarcerated placenta. Following delivery, the first Methergine tablet (0.25 mg.) was given orally in about four to six: hours, and repeated three times daily for two days unless more was thought necessary due to excessive bleeding. The latter was the exception rather than the rule. From the birth of the child to the time when the patient was taken down from the stirrups, all the blood lost vaginally, including that from the episiotomy, was collected in a sterile basin, held below the buttocks, and measured. Duration of the Third Stage A short third stage was characteristic of this series. As a rule, the first contraction after the intravenous use of Methergine was exceptionally forceful. After expression of the placenta, the uterus became very hard and round, maintained this tone for several hours, and could be palpated more often in the midline than to one side. By the time the patient's legs were off the stirrups, there was usually only a slight trickle of blood from the vagina and, i£ the fundus of the uterus was held abdominally between the palms of both hands for fifteen to twenty minutes, this status quo lasted until the action of Methergine had worn off hours later. The shortest third stage was one minute, with one exception, when the placenta was expressed with a stillborn fetus. The longest duration was fortyone minutes, giving a mean average of four and one-half minutes. The average length of the third stage in primiparas was 3.2 minutes, and in multiparas 4.6 minutes. 1065
Am. j. Ol,t, & Gyne,·.
GIPS'rEIN
1066
December, 194 7
The length of the third stage in 157 cases ( 87.2 per eent) was np to five minutes. In 18 cases (10.0 per cent), it was between six to fifteen minutes, and in five cases (2.8 per cent) it was between sixteen to forty-one minutes. TABLE I
I'El!CENTMIE
CASES
157
0 to ::i (i to 13
18 5
87.2 10.0
16 to 41 ---
Blood Loss in Third Stage It is interesting to note that one-half of this series fell into the group where the blood loss ranged between 50 to 100.
60 to lOll 101 to 449 450 and over
40 17 ()
II
:i4.K
:.J:U 0.0
GO
10 7
46.8 9.3 6.5 100.0
A brief review of three cases who lost more than 50 c.c. and less than 450 c.c. is presented: CASE No. 2l.~R. A., aged 26 years, pata i. Pressure on admission 200/100, postpartum 76/66. Bclampsia with abruptio. Outlet forceps and episiotomy. Morbidity 99.2 to 100.0. Postpartum shock. Uterus five fingers above symphysis immediately post partum, and one fingerbreadth above symphysis on discharge. Placenta delivered with stillborn. Scant serous lochia throughout. No abdominal pain throughout. Measured blood loss third stage 200 c.c. The complicating toxemia and premature detachment of the placenta were, no doubt, responsible for the greater blood loss. CASE No. 64.~-C. B., aged 24 years, para i. Midforceps and episiotomy. Pressure on admission 100/62, after delivery 98/68. Placenta expressed after thirty-five minutes incarceration by cervix (removal spontaneous). No morbidity. Uterus six fingers above symphysis after delivery, and two fingers above on discharge. Slight pain (cramps) first day. Spotting after third day. Measured blood loss 200 c.c., probably a result of retained placenta. CASE No. 82.-S. S., aged 34 years, para viii. Spontaneous delivery. Blood pressure on admission 130/92, after delivery 110/70. Retained, adherent placenta with manual removal. Uterus six fingers above symphysis after delivery, and two and one-half fingers on discharge. No morbidity. Spotting after third day. Slight cramps during first two days. Measured blood loss 100 c.c.
Volume 54 Number 6
CLINICAL USE OF MJ;;THERGINE
1067
Blood Loss Over 450 Cubic Centimeters CAsE No. 4.-A. S., aged 31 years, para ii. Outlet forceps and episiotomy. Blood pressure 124/60 to 118/64. Membranes ruptured mechanically when fully dilated. Uterus atonic after five minutes at the end of the third stage, and second ampule of Methergine was given intramuscularly, followed by firm contraction with massage. No morbidity. Slight cramps on first day. Placenta delivered in three minutes. No flow on tenth day. Uterus six fingers above symphysis after delivery, and three fingers above on discharge. Blood loss 500 c.c. The reason for this amount of bleeding is obscure. CASE No. 15.-A. M., aged 2fi years, para iv. Blood pressure 112/78 to 120/82. Outlet forceps, no episiotomy. Gush of blood with birth of head. Several clots after expression of placenta in two minutes, and second ampule of Methergine was given intramuscularly. No morbidity. Uterus six fingers above symphysis after delivery and one and one-half fingers above on discharge. Cramps on first day. Scant spotting on tenth day. Blood loss measured 500 cubic centimeters. CASE No. 59.-J. R., aged 24 years, para ii (Dr. M.F.G.). Outlet forceps, left episiotomy. Blood pressure 122/78. Placenta expressed in three minutes. No morbidity. No cramps. Very slight flow on discharge. Measured blood loss 500 c.c. probably due to bleeding vessel in episiotomy. CASE No. 62.-E. M. L., aged 32 years, para iii (Dr. M.F.G.). Spontaneous delivery. Placenta expressed in four minutes. Two ampules Methergine given intravenously. Slight cramps first two days. No morbidity. No flow after third day. Uterus six fingers above symphysis after delivery, and three above on discharge. Measured blood loss 800 c.c., due in part to laceration through scar tissue.
Postpartum Pain and Lochia About one-half the patients, more especially the multiparas, complained of slight cramps on the first postpartum day. These cramps started about fifteen to twenty minutes after receiving their first Methergine tablet, and lasted from one-half to two hours. No one eomplained of afterpains after the seeond day. Generally, postpartum pain was much less, and the uterus was less tender than when other oxytocies were used. Each day the size of the contracted uterus could be felt at a lower level, so that by the eighth postpartum day it could be palpated at between one to two finger breadths above the symphysis. To date, there have been no postpartum hemorrhages in this series, nor has any woman had a ''gush of blood'' oJt getting out of bed. Eleven cases, or 5 per cent, had an elevation of temperature of 99.4° F. or more for two consecutive days. These could be further corre-cted if we take into consideration that elevation in temperature was connected with full and engorged breasts. Except for occasional irregular spotting after leaving the hospital, most patients had a thin lochia, after the third or fourth day post partum, devoid of a foul odor. By the time of their six-week check-up the uterus was completely involuted. There was less complaint of low backache; the red cell count showed no more than a mild hypochromic anemia; and their general physical condition was good. Summary A series of 180 cases are presented in which a new synthetic drug, .Ylethergine, was used. The third stage of labor was appreciably shortened. The blood loss in the third stage was decreased.
lOGS
GIPSTEIN
Am.]. Ob,t. & Gynec. December, 1947
The prolonged action of the drug required less medication post partum. Postpartum bleeding and the umount of the lochia was decreased. Irwolution took place sooner· and the general condition of the patient was enhanced by its judicious nsc.
Conclusion 1\fethergine is a new synthetic oxytocic which seems to be very effective and safe when used in the third stage of labor. I wish to express my thanks to Bandoz Chemical Works, Inc., who supplied both the ampules and tablets o:f Methergine used in this eeries. To the Sisters of Providence and the nurses at the Mercy Hospital, and to Dr. Milton F. Gipstein, I express my gratitude for their cooperation and help in r~olleding r1ata.
References Cartwright, E. W., and Rogers, W. C.: West. J. Surg. 54: 59, 1946. Bepp. L. C., and Evans, J. R.: Rocky Mountain M . .J. 42: 949, 1945. Kirchhof, A. C., Racely, C. A .. Wilson, W. M., and David, N. A.: West. J. Surg. 52: 197, 1944. Kirchhof, A. C., Phatak, N. M., and Racely, C. A.: Federation Proceedings 3: 76, 1944. Robert~, P. C.: West. J. Surg. 52: 380, 1944. 'Stoll, A., and Hofmann, A.: Helvetica Chimica Acta 26; 944, 194:3. TollefRon, D. G.: West. J. Surg. 52: 383, 1944. Tritsch, J. E., and Schneider, E.: AM. ,T. OBST. & GYNEC. 50: 434, 1945.