InlJ Gynaecol Obstei 17: 281-283, 1979
Diazepam Therapy in Eclampsia C. S. Dawn 1 and B. Sinha 2 2
Department of Obstetrics and Gynaecology, Medical College, Calcutta, India Department of Obstetrics and Gynaecology, Bankura Sanmilani Medical College, Bankura, West Bengal, India
ABSTRACT Dawn CS, Sinha B (Dept of Obstetrics and Gynaecology, Medical College, Calcutta, India, and Dept of Obstetrics and Gynaecology, Bankura Sanmilani Medical College, Bankura, West Bengal, India). Diazepam therapy in eclampsia. IntJ Gynaecol Obstet 17: 281-283, 1979 The single drug therapy of diazepam can be introduced to effectively control convulsions in eclampsia. This treatment will have particular application in rural obstetrics where eclampsia is seen in severe form. The dose schedule of diazepam, as described in this study, shows the therapy to have a stabilizing effect on hypertension and pulse rate. It causes neither respiratory depression nor oliguria. Diazepam is an effective muscle relaxant. Its depressive effect on the newborn is in no way inferior to that of lytic cocktail therapy. The drug is readily available at low cost, even in the remote rural areas, and can be easily administered by any doctor or midwife.
INTRODUCTION Newer anticonvulsant and hypotensive drugs have been used over the last four decades, ever since Stroganoff (5) showed that an eclamptic patient needs sedatives as basic treatment. T h e sedatives and anticonvulsants used were morphia, chloral hydrate, bromide, magnesium sulfate, paraldehyde, bromethol, thiopental sodium and phenothiazine (lytic cocktail). In 1968, Lean et al (3) used diazepam as an anticonvulsant to treat eclampsia. T h e antihypertensives used as adjunctive therapy were veratrum, rauwolfia and hydralazine. T h e value of the introduction of diazepam to treat eclampsia is reviewed from experience in a rural obstetric practice in West Bengal. MATERIALS A N D M E T H O D S O n e hundred forty-one (141) eclamptic patients were treated at the Bankura Sanmilani Medical
College Hospital, Bankura, West Bengal, between July 1, 1975, and J u n e 30, 1977. This center serves the rural population of the three neighboring districts. Occasionally, an eclamptic patient was transported on a bullock cart from a remote corner of the district to the nearest health center and was then transferred to our hospital by ambulance. At the health center, an eclamptic patient was injected with either morphine or chlorpromazine and promethazine hydrochloride before being transported to the hospital. T h e majority of the patients were antepartum or intrapartum and thus arrived at the hospital in severe eclamptic states having h a d several convulsions during the transport. O n admission, the patient was placed in a special room that was air conditioned during the summer months. Diazepam therapy Unit I of our department administered the diazepam therapy. Fifty-five (55) patients were treated with diazepam therapy. Each patient was given a single intravenous injection of 20 mg of diazepam followed by 100 mg of pethidine hydrochloride in a pint of 5% dextrose drip. A second pint of dextrose with another 100 mg of pethidine was infused within 12 hours. An intramuscular injection of 20 m g of diazepam was given within one hour of the intravenous injection and thereafter repeated every four to six hours as needed for 48 hours. If convulsions were not controlled by two injections, the third dose was given within the second hour. Supportive treatment included electric suction of the throat, supplemental oxygen, furosemide given intravenously for pulmonary edema and antibiotics. Nursing and medical care was continuous. Lytic cocktail therapy Unit II of our department administered the lytic cocktail therapy, treating 86 patients. O n admission, each patient received 25 mg of chlorpromazine, injected intravenously. This was followed by infusion of one pint of 5% dextrose loaded with 100 m g
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of injectable pethidine hydrochloride; a second pint of the same mixture followed. An intramuscular injection of 25 m g of chlorpromazine and 25 m g of promethazine hydrochloride was given at the end of the first hour. This was followed by repeated injections of 25 mg of chlorpromazine and 25 mg of promethazine hydrochloride every four to six hours as needed. This sedative treatment was continued until delivery. Obstetric management T h e first vaginal examination was performed one hour after admission when the patient was sedated. A catheter was fitted and clipped to measure the urinary output. After 12 hours, the cervix was reassessed. Some patients were in labor at the time of admission. Others began spontaneous labor within 12 hours of admission; in these patients, the membranes were ruptured when the eclamptic convulsions were controlled. In the remaining patients, at the second assessment, artificial rupture of the membranes was performed to induce labor after the eclamptic convulsions were controlled. All the latter patients went into labor. No cesarean section deliveries occurred. All patients were delivered spontaneously or by operative procedure, such as forceps, vacuum extraction or a destructive operation, within 24 hours of admission. Each patient's vital signs, complications and urine volume, together with the status of the baby, were carefully recorded on a printed form. Follow-up treatment After delivery, the patients who had diazepam therapy were given 5 mg of diazepam orally thrice, twice or nightly until the time of discharge. T h e patients under the lytic cocktail regime received 60 mg of phénobarbital orally following delivery. Clinical classification Eclampsia was classified as (a) severe, when there were more than ten convulsions and the blood pressure was above 180/130 mm H g and (b) mild, when there were ten or fewer convulsions and blood pressure ranged between 140/90 and 180/130 m m Hg.
RESULTS Distributions of the age and parity of the patients and the severity and timing of the eclampsia in the diazepam and lytic cocktail groups were comparable (Tables I and II).
IntJ Gynaecol Obstet 17
Table I. Age and parity distributions of eclamptic patients on diazepam and lytic cocktail therapy. Patients on Lytic Patients on Diazepam Therapy Cocktail Therapy (N = 86) (N = 55) Age (years) 15-19 >19
41 (75%) 14 (25%)
60 (70%) 24 (30%)
Parity 0 1-3
50 (90%) 5(10%)
72 (85%) 14(15%)
Table II. Severity and timing of eclampsia in patients on diazepam and lytic cocktail therapy. Patients on Diazepam Therapy (N = 55)
Patients on Lytic Cocktail Therapy (N = 86)
Degree of Severity Severe Mild
38 (69%) 17(31%)
56 (65%) 30 (35%)
Timing Antepartum Intrapartum Postpartum
4 4 (80%) 3 (6%) 8 (15%)
6 0 (70%) 10(14%) 14(16%)
Immediate control of convulsions occurred in 43 (80%) of the patients on diazepam therapy and in 51 (60%) of the lytic cocktail group. Control of convulsions was possible on diazepam therapy in all cases within four hours, but was not possible on lytic cocktail therapy in eight cases. Blood pressure showed a gradual fall from above 180/130 to below 140/90 mm H g in 48 hours in the patients receiving diazepam. T h e pulse rates of these patients stabilized (mean pulse rate on admission was 137 ± 12; at 24 hours after admission, 104 ± 9; at 48 hours, 99 ± 8). In the diazepam group, 47 (85%) patients had a urinary output above 1000 m l / 24 hours. Drowsiness was noted in the patients on the diazepam. Complications occurring in both therapy groups are shown in T a b l e III. T h e complication rate appears significantly lower in the diazepam group. One patient under diazepam therapy and six patients under lytic cocktail therapy died undelivered within six hours of admission. Of the 55 patients on diazepam therapy, five (9.0%) died. There were eight stillbirths, and five babies died in their first week in the group of mothers on diazepam, for
Diazepam therapy in eclampsia
Table III. Patients with complications in the two therapy groups.
Complications Pulmonary edema Temperature > 105 F Oliguria Psychosis Total
Patients on Diazepam Therapy (N = 55)
Patients on Lytic Cocktail Therapy (N = 86)
6 3 1 1 11 (20%)
12 8 3 11 34 (51 %)
a perinatal mortality of 29.6%. Of the 86 eclamptic patients treated by lytic cocktail therapy, 15 (17.5%) died; the perinatal mortality was 26 (30.0%), of which 17 were stillbirths and nine were infant deaths occurring in the first week. This result shows significant lowering of maternal mortality under diazepam therapy although there is no difference in perinatal mortality.
DISCUSSION In this sample, none of the eclamptic patients had antenatal care. T w o thirds of them were severely eclamptic, a n d thus there was high maternal mortality, as high as 17.5% in the lytic cocktail therapy group. This may be compared to the 2.4% reported by Menon (4). T h e maternal mortality of 9.0% under the diazepam therapy in this series is a result of the high proportion of severely affected rural eclamptic patients. Lean et al (3) in Singapore showed a lower maternal mortality of 3.3%, since the Singapore sample was by a n d large urban a n d therefore less severely affected. Kawathekar (2) from Gulbarga, Karnataka, showed one maternal death in 30 patients treated by diazepam therapy, but there were few severe cases in her series. Goodman and Gilman (1) opined that diazepam, belonging to the benzodiazepine group, acts as an effective anticonvulsant by cortical and spinal reflex depression. It is also a muscle relaxant a n d a hypnotic. They further asserted that the solvent for the commercial parenteral preparation is a propylene-glycol-
283
ethanol-water mixture a n d should not be diluted with aqueous solution. This series shows that diazepam in therapeutic parenteral dosage does not depress cardiovascular and respiratory systems. Moreover, it acts as an antihypertensive. T h e convulsions and excitability of an eclamptic patient abate immediately on intravenous injection of 20 mg of diazepam. T h e patient becomes sedated and relaxed. Its effect on the newborn does not significantly differ from that seen in the lytic cocktail therapy. This low-cost drug is available at the rural centers in our country, is easily handled by any doctor and is less expensive than lytic cocktail therapy.
ACKNOWLEDGMENT T h e authors are grateful to Professor J. Das, Dean, Bankura Sanmilani Medical College Hospital, Bankura, West Bengal, India, for his kind permission to publish this work. T h e authors are also indebted to all the consultants, residents a n d nursing staff of the Department of Obstetrics and Gynaecology for their support.
REFERENCES . 1. Goodman LS, Gilman A: The Pharmacological Basis of Therapeutics, 5th ed. Macmillan, New York, 1975. 2. Kawathekar P: Diazepam in eclampsia. J Obstet Gynaecol India 26(3):351, 1976. 3. Lean TH, Ratnam SS, Sivasamboo R: The use of benzodiazepines in eclampsia. J Obstet Gynaecol Br Commonw 75:856, 1968. 4. Menon MK: Obstetrics in India. In Modern Trends in Obstetrics, 4th ed (ed RJ Kellar), p 301. Butterworth, London, 1969. 5. Stroganoff W: The improved prophylactic method in treatment of eclampsia. Livingstone, Edinburgh, 1930.
Address for reprints: C. S. Dawn Dept of Obstetrics and Gynaecology Medical College Calcutta, India
IntJ Gynaecol Obstet 17
Diazepam Therapy in Eclampsia C. S. Dawn 1 and B. Sinha 2 2
Department of Obstetrics and Gynaecology, Medical College, Calcutta, India Department of Obstetrics and Gynaecology, Bankura Sanmilani Medical College, Bankura, West Bengal, India
ABSTRACT Dawn CS, Sinha B (Dept of Obstetrics and Gynaecology, Medical College, Calcutta, India, and Dept of Obstetrics and Gynaecology, Bankura Sanmilani Medical College, Bankura, West Bengal, India). Diazepam therapy in eclampsia. IntJ Gynaecol Obstet 17: 281-283, 1979 The single drug therapy of diazepam can be introduced to effectively control convulsions in eclampsia. This treatment will have particular application in rural obstetrics where eclampsia is seen in severe form. The dose schedule of diazepam, as described in this study, shows the therapy to have a stabilizing effect on hypertension and pulse rate. It causes neither respiratory depression nor oliguria. Diazepam is an effective muscle relaxant. Its depressive effect on the newborn is in no way inferior to that of lytic cocktail therapy. The drug is readily available at low cost, even in the remote rural areas, and can be easily administered by any doctor or midwife.
INTRODUCTION Newer anticonvulsant and hypotensive drugs have been used over the last four decades, ever since Stroganoff (5) showed that an eclamptic patient needs sedatives as basic treatment. T h e sedatives and anticonvulsants used were morphia, chloral hydrate, bromide, magnesium sulfate, paraldehyde, bromethol, thiopental sodium and phenothiazine (lytic cocktail). In 1968, Lean et al (3) used diazepam as an anticonvulsant to treat eclampsia. T h e antihypertensives used as adjunctive therapy were veratrum, rauwolfia and hydralazine. T h e value of the introduction of diazepam to treat eclampsia is reviewed from experience in a rural obstetric practice in West Bengal. MATERIALS A N D M E T H O D S O n e hundred forty-one (141) eclamptic patients were treated at the Bankura Sanmilani Medical
College Hospital, Bankura, West Bengal, between July 1, 1975, and J u n e 30, 1977. This center serves the rural population of the three neighboring districts. Occasionally, an eclamptic patient was transported on a bullock cart from a remote corner of the district to the nearest health center and was then transferred to our hospital by ambulance. At the health center, an eclamptic patient was injected with either morphine or chlorpromazine and promethazine hydrochloride before being transported to the hospital. T h e majority of the patients were antepartum or intrapartum and thus arrived at the hospital in severe eclamptic states having h a d several convulsions during the transport. O n admission, the patient was placed in a special room that was air conditioned during the summer months. Diazepam therapy Unit I of our department administered the diazepam therapy. Fifty-five (55) patients were treated with diazepam therapy. Each patient was given a single intravenous injection of 20 mg of diazepam followed by 100 mg of pethidine hydrochloride in a pint of 5% dextrose drip. A second pint of dextrose with another 100 mg of pethidine was infused within 12 hours. An intramuscular injection of 20 m g of diazepam was given within one hour of the intravenous injection and thereafter repeated every four to six hours as needed for 48 hours. If convulsions were not controlled by two injections, the third dose was given within the second hour. Supportive treatment included electric suction of the throat, supplemental oxygen, furosemide given intravenously for pulmonary edema and antibiotics. Nursing and medical care was continuous. Lytic cocktail therapy Unit II of our department administered the lytic cocktail therapy, treating 86 patients. O n admission, each patient received 25 mg of chlorpromazine, injected intravenously. This was followed by infusion of one pint of 5% dextrose loaded with 100 m g
IntJ Gynaecol Obstet 17
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Dawn and Sinha
of injectable pethidine hydrochloride; a second pint of the same mixture followed. An intramuscular injection of 25 m g of chlorpromazine and 25 m g of promethazine hydrochloride was given at the end of the first hour. This was followed by repeated injections of 25 mg of chlorpromazine and 25 mg of promethazine hydrochloride every four to six hours as needed. This sedative treatment was continued until delivery. Obstetric management T h e first vaginal examination was performed one hour after admission when the patient was sedated. A catheter was fitted and clipped to measure the urinary output. After 12 hours, the cervix was reassessed. Some patients were in labor at the time of admission. Others began spontaneous labor within 12 hours of admission; in these patients, the membranes were ruptured when the eclamptic convulsions were controlled. In the remaining patients, at the second assessment, artificial rupture of the membranes was performed to induce labor after the eclamptic convulsions were controlled. All the latter patients went into labor. No cesarean section deliveries occurred. All patients were delivered spontaneously or by operative procedure, such as forceps, vacuum extraction or a destructive operation, within 24 hours of admission. Each patient's vital signs, complications and urine volume, together with the status of the baby, were carefully recorded on a printed form. Follow-up treatment After delivery, the patients who had diazepam therapy were given 5 mg of diazepam orally thrice, twice or nightly until the time of discharge. T h e patients under the lytic cocktail regime received 60 mg of phénobarbital orally following delivery. Clinical classification Eclampsia was classified as (a) severe, when there were more than ten convulsions and the blood pressure was above 180/130 mm H g and (b) mild, when there were ten or fewer convulsions and blood pressure ranged between 140/90 and 180/130 m m Hg.
RESULTS Distributions of the age and parity of the patients and the severity and timing of the eclampsia in the diazepam and lytic cocktail groups were comparable (Tables I and II).
IntJ Gynaecol Obstet 17
Table I. Age and parity distributions of eclamptic patients on diazepam and lytic cocktail therapy. Patients on Lytic Patients on Diazepam Therapy Cocktail Therapy (N = 86) (N = 55) Age (years) 15-19 >19
41 (75%) 14 (25%)
60 (70%) 24 (30%)
Parity 0 1-3
50 (90%) 5(10%)
72 (85%) 14(15%)
Table II. Severity and timing of eclampsia in patients on diazepam and lytic cocktail therapy. Patients on Diazepam Therapy (N = 55)
Patients on Lytic Cocktail Therapy (N = 86)
Degree of Severity Severe Mild
38 (69%) 17(31%)
56 (65%) 30 (35%)
Timing Antepartum Intrapartum Postpartum
4 4 (80%) 3 (6%) 8 (15%)
6 0 (70%) 10(14%) 14(16%)
Immediate control of convulsions occurred in 43 (80%) of the patients on diazepam therapy and in 51 (60%) of the lytic cocktail group. Control of convulsions was possible on diazepam therapy in all cases within four hours, but was not possible on lytic cocktail therapy in eight cases. Blood pressure showed a gradual fall from above 180/130 to below 140/90 mm H g in 48 hours in the patients receiving diazepam. T h e pulse rates of these patients stabilized (mean pulse rate on admission was 137 ± 12; at 24 hours after admission, 104 ± 9; at 48 hours, 99 ± 8). In the diazepam group, 47 (85%) patients had a urinary output above 1000 m l / 24 hours. Drowsiness was noted in the patients on the diazepam. Complications occurring in both therapy groups are shown in T a b l e III. T h e complication rate appears significantly lower in the diazepam group. One patient under diazepam therapy and six patients under lytic cocktail therapy died undelivered within six hours of admission. Of the 55 patients on diazepam therapy, five (9.0%) died. There were eight stillbirths, and five babies died in their first week in the group of mothers on diazepam, for
Diazepam therapy in eclampsia
Table III. Patients with complications in the two therapy groups.
Complications Pulmonary edema Temperature > 105 F Oliguria Psychosis Total
Patients on Diazepam Therapy (N = 55)
Patients on Lytic Cocktail Therapy (N = 86)
6 3 1 1 11 (20%)
12 8 3 11 34 (51 %)
a perinatal mortality of 29.6%. Of the 86 eclamptic patients treated by lytic cocktail therapy, 15 (17.5%) died; the perinatal mortality was 26 (30.0%), of which 17 were stillbirths and nine were infant deaths occurring in the first week. This result shows significant lowering of maternal mortality under diazepam therapy although there is no difference in perinatal mortality.
DISCUSSION In this sample, none of the eclamptic patients had antenatal care. T w o thirds of them were severely eclamptic, a n d thus there was high maternal mortality, as high as 17.5% in the lytic cocktail therapy group. This may be compared to the 2.4% reported by Menon (4). T h e maternal mortality of 9.0% under the diazepam therapy in this series is a result of the high proportion of severely affected rural eclamptic patients. Lean et al (3) in Singapore showed a lower maternal mortality of 3.3%, since the Singapore sample was by a n d large urban a n d therefore less severely affected. Kawathekar (2) from Gulbarga, Karnataka, showed one maternal death in 30 patients treated by diazepam therapy, but there were few severe cases in her series. Goodman and Gilman (1) opined that diazepam, belonging to the benzodiazepine group, acts as an effective anticonvulsant by cortical and spinal reflex depression. It is also a muscle relaxant a n d a hypnotic. They further asserted that the solvent for the commercial parenteral preparation is a propylene-glycol-
283
ethanol-water mixture a n d should not be diluted with aqueous solution. This series shows that diazepam in therapeutic parenteral dosage does not depress cardiovascular and respiratory systems. Moreover, it acts as an antihypertensive. T h e convulsions and excitability of an eclamptic patient abate immediately on intravenous injection of 20 mg of diazepam. T h e patient becomes sedated and relaxed. Its effect on the newborn does not significantly differ from that seen in the lytic cocktail therapy. This low-cost drug is available at the rural centers in our country, is easily handled by any doctor and is less expensive than lytic cocktail therapy.
ACKNOWLEDGMENT T h e authors are grateful to Professor J. Das, Dean, Bankura Sanmilani Medical College Hospital, Bankura, West Bengal, India, for his kind permission to publish this work. T h e authors are also indebted to all the consultants, residents a n d nursing staff of the Department of Obstetrics and Gynaecology for their support.
REFERENCES . 1. Goodman LS, Gilman A: The Pharmacological Basis of Therapeutics, 5th ed. Macmillan, New York, 1975. 2. Kawathekar P: Diazepam in eclampsia. J Obstet Gynaecol India 26(3):351, 1976. 3. Lean TH, Ratnam SS, Sivasamboo R: The use of benzodiazepines in eclampsia. J Obstet Gynaecol Br Commonw 75:856, 1968. 4. Menon MK: Obstetrics in India. In Modern Trends in Obstetrics, 4th ed (ed RJ Kellar), p 301. Butterworth, London, 1969. 5. Stroganoff W: The improved prophylactic method in treatment of eclampsia. Livingstone, Edinburgh, 1930.
Address for reprints: C. S. Dawn Dept of Obstetrics and Gynaecology Medical College Calcutta, India
IntJ Gynaecol Obstet 17
