- Email: [email protected]
Efficacy of phenytoin in eclampsia
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GYNECOLOGY &OBSTETRIC3 International
Journal
of Gynecology
& Obstetrics
56 (1997)
275-276
Brief communication
Efficacy of phenytoin in eclampsia S. Naidu, J. Moodley” MRC/
UN Pregnancy
Hyertension
Received
Kqwordr:
Eclampsia;
Research
31 January
Phenytoin;
Unit, Faculty
1996; revised
of Medicine,
20 November
0020-7292/97/$17.00 PZZSOO20-7292(96)
author.
Fax:
1996; accepted
of Natal, 25 November
Durban,
South Africa
1996
Seizures
The pathophysiology of eclampsia is poorly understood and treatment controversial. Despite this, the primary goals of therapy include lowering high blood pressure and prevention of seizures. A review of the world literature however, indicates considerable debate regarding the ideal prophylactic anticonvulsant in eclampsia. Recently, the Eclampsia Trial Collaborative Group [l], reported that MgSO, was more effective in preventing recurrent convulsions in eclampsia than phenytoin, and Lucas et al. [2] have reported that magnesium sulfate is superior to phenytoin for the prevention of eclampsia. Nonetheless, confirmatory evidence that phenytoin is not useful as a prophylactic agent in eclampsia is necessary. The aim of this study was to assess the efficacy of phenytoin in the control and prevention of seizures in eclampsia. Sixty-eight patients admitted to the obstetric unit with a diagnosis of eclampsia were included in the study. Eclampsia was defined as seizures associated with hypertension and proteinuria. On entry to the study, all patients were managed by standard methods previously described [3]. Di-
*Corresponding [email protected].
University
27
031
Q 1997 International 02833-o
2604428;
Federation
e-mail:
of Gynecology
azepam was given to abort eclamptic fits on admission and phenytoin was only commenced after the patient was stabilized. A loading dose of 1000 mg of phenytoin sodium (Epanutin, ParkeDavis), diluted in 200 ml of normal saline was infused as an intravenous ‘piggy-back arrangement’ over 15-20 min. Maintenance doses of 100 mg were given intravenously at 6-h intervals for 24 h. During the infusion of the loading dose, the electrocardiogram (Lead II) was monitored continuously for arrhythmias. Blood pressure levels and heart rate were measured every 5 min during infusion of the loading dose of phenytoin by means of a non-invasive automatic blood pressure recorder (Dinamap). The clinical and demographic data of all patients are shown in Table 1. Ten patients required intravenous dihydralazine either prior to, or during phenytoin infusion. There were eight neonatal deaths; seven due to complications of prematurity and the other from birth - asphyxia. There were 18 (26.5%) (95% CI: 16-37%) who had recurrent eclamptic seizures following phenytoin therapy. In 16, recurrence of seizures occurred between the time of the loading dose and maintenance dose at 6 h. Six patients had further convulsions following their first maintenance dose. and Obstetrics
276
S. Naidu,
J. Moodeb
/International
Journal
Table 1 Clinical data and obstetric outcome of all patients (n = 68);values shown are mean (range) or number (%) Mean Range Age (years) Parity
23 0 21 Gestational age (weeks) 33 BP CmmHgl - systolic 163 - diastolic 110 Proteinuria 3+ 12 GCSa No. of convulsions 2
Timing of convulsions: - antepartum 45 - intrapartum 17 - postpartum 6 Cesarean section 51 Birth weight (g) 2124 Fetal outcome: stillbirth 11 live 48 NNlY 8 Apgar score: 1 min 56 27 5 min 16 r 7 Recurrence of seizures 18 Maternal mortality 4
(14-43) 48.5% 57.5% (20-39)
Standard deviation 6.8
(110-210) 23.9 (70-150) 18.3 (O-4) 0.9 (3-15) l-37.1% 2-22.6% 2 3-40.370 (66%) (25%) (7:;) (400-3100) (16.9%) (68.8%) (12.3%) (64.3%) (35.7%) (17%) (83%) (26.5%) (5.9%)
GCS, Glasgow coma scale; NND, neonatal death. aRepresented as proportions.
The mean blood pressure at the time of seizure recurrence was 185/110 mmHg. In one patient who had nine recurrent seizures unresponsive to phenytoin, magnesium sulfate was commenced and there were no further convulsions. There were 4 maternal deaths in this series; one had pulmonary edema and the other 3 adult respiratory distress syndrome; all 4 had required assisted ventilation. Most studies advocating the use of prophylactic phenytoin involved patients with mild or moderate pre-eclampsia in whom anticonvulsant therapy may not be of value. These studies also had small numbers of patients which did not allow an assessment of the efficacy of seizure prevention.
of Gynecology
& Obstetrics
56 (1997) 275-276
The present study included a large series of patients with eclampsia (n = 68). Eighteen patients in this study required ventilatory support and the mean Glasgow coma scale was 12, indicating the severity of the condition of patients studied. The clinical characteristics of the 18 patients who had seizures following phenytoin were similar to those who did not have recurrent convulsions. No single clinical characteristic predicted recurrence of seizures. In all phenytoin ‘failures’ in this study, there were no focal neurological signs on admission and at a 6-week follow-up. The incidence of subsequent convulsions in eclamptic women receiving phenytoin was 26.5% which is considerably higher than the 10% reported by Sibai, in patients receiving MgSO, [4]. We conclude that seizure recurrence following phenytoin therapy in eclampsia is unacceptably high. The poor performance of phenytoin as an anticonvulsant in eclampsia may be due to severe cerebral vasospasm resulting in inadequate phenytoin levels in the brain to effect its anticonvulsant activity. An effective cerebral vasodilator may be a better choice for seizure prevention in eclampsia than a drug that primarily suppresses seizure foci. The results of this descriptive study add to the evidence of the large randomized clinical trial performed by the Eclampsia Trial Collaborative Group, comparing the safety and efficacy of these drugs in a homogeneous group of women with eclampsia. References
111 Eclampsia Trial Collaborative Group. Which anticonvulsant for women with eclampsia? Evidence from the Collaborative Eclampsia Trial. Lancet 1995; 345: 1455-1463. El Lucas MI, Levine KJ, Cunningham FG. A comparison of magnesium sulphate with phenytoin for the prevention of eclampsia. N Engl J Med 1995; 333: 201-205. [31 Moodley J, Naicker RS, Mankowitz E. Eclampsia - a methodof management. S Afr Med J 1983; 63: 530-535. [41 Sibai BM. Magnesium sulphate is the ideal anticonvulsant in pre-eclampsia-eclampsia. Am J Obstet Gynecol 1990; 162: 1141-1145.
GYNECOLOGY &OBSTETRIC3 International
Journal
of Gynecology
& Obstetrics
56 (1997)
275-276
Brief communication
Efficacy of phenytoin in eclampsia S. Naidu, J. Moodley” MRC/
UN Pregnancy
Hyertension
Received
Kqwordr:
Eclampsia;
Research
31 January
Phenytoin;
Unit, Faculty
1996; revised
of Medicine,
20 November
0020-7292/97/$17.00 PZZSOO20-7292(96)
author.
Fax:
1996; accepted
of Natal, 25 November
Durban,
South Africa
1996
Seizures
The pathophysiology of eclampsia is poorly understood and treatment controversial. Despite this, the primary goals of therapy include lowering high blood pressure and prevention of seizures. A review of the world literature however, indicates considerable debate regarding the ideal prophylactic anticonvulsant in eclampsia. Recently, the Eclampsia Trial Collaborative Group [l], reported that MgSO, was more effective in preventing recurrent convulsions in eclampsia than phenytoin, and Lucas et al. [2] have reported that magnesium sulfate is superior to phenytoin for the prevention of eclampsia. Nonetheless, confirmatory evidence that phenytoin is not useful as a prophylactic agent in eclampsia is necessary. The aim of this study was to assess the efficacy of phenytoin in the control and prevention of seizures in eclampsia. Sixty-eight patients admitted to the obstetric unit with a diagnosis of eclampsia were included in the study. Eclampsia was defined as seizures associated with hypertension and proteinuria. On entry to the study, all patients were managed by standard methods previously described [3]. Di-
*Corresponding [email protected].
University
27
031
Q 1997 International 02833-o
2604428;
Federation
e-mail:
of Gynecology
azepam was given to abort eclamptic fits on admission and phenytoin was only commenced after the patient was stabilized. A loading dose of 1000 mg of phenytoin sodium (Epanutin, ParkeDavis), diluted in 200 ml of normal saline was infused as an intravenous ‘piggy-back arrangement’ over 15-20 min. Maintenance doses of 100 mg were given intravenously at 6-h intervals for 24 h. During the infusion of the loading dose, the electrocardiogram (Lead II) was monitored continuously for arrhythmias. Blood pressure levels and heart rate were measured every 5 min during infusion of the loading dose of phenytoin by means of a non-invasive automatic blood pressure recorder (Dinamap). The clinical and demographic data of all patients are shown in Table 1. Ten patients required intravenous dihydralazine either prior to, or during phenytoin infusion. There were eight neonatal deaths; seven due to complications of prematurity and the other from birth - asphyxia. There were 18 (26.5%) (95% CI: 16-37%) who had recurrent eclamptic seizures following phenytoin therapy. In 16, recurrence of seizures occurred between the time of the loading dose and maintenance dose at 6 h. Six patients had further convulsions following their first maintenance dose. and Obstetrics
276
S. Naidu,
J. Moodeb
/International
Journal
Table 1 Clinical data and obstetric outcome of all patients (n = 68);values shown are mean (range) or number (%) Mean Range Age (years) Parity
23 0 21 Gestational age (weeks) 33 BP CmmHgl - systolic 163 - diastolic 110 Proteinuria 3+ 12 GCSa No. of convulsions 2
Timing of convulsions: - antepartum 45 - intrapartum 17 - postpartum 6 Cesarean section 51 Birth weight (g) 2124 Fetal outcome: stillbirth 11 live 48 NNlY 8 Apgar score: 1 min 56 27 5 min 16 r 7 Recurrence of seizures 18 Maternal mortality 4
(14-43) 48.5% 57.5% (20-39)
Standard deviation 6.8
(110-210) 23.9 (70-150) 18.3 (O-4) 0.9 (3-15) l-37.1% 2-22.6% 2 3-40.370 (66%) (25%) (7:;) (400-3100) (16.9%) (68.8%) (12.3%) (64.3%) (35.7%) (17%) (83%) (26.5%) (5.9%)
GCS, Glasgow coma scale; NND, neonatal death. aRepresented as proportions.
The mean blood pressure at the time of seizure recurrence was 185/110 mmHg. In one patient who had nine recurrent seizures unresponsive to phenytoin, magnesium sulfate was commenced and there were no further convulsions. There were 4 maternal deaths in this series; one had pulmonary edema and the other 3 adult respiratory distress syndrome; all 4 had required assisted ventilation. Most studies advocating the use of prophylactic phenytoin involved patients with mild or moderate pre-eclampsia in whom anticonvulsant therapy may not be of value. These studies also had small numbers of patients which did not allow an assessment of the efficacy of seizure prevention.
of Gynecology
& Obstetrics
56 (1997) 275-276
The present study included a large series of patients with eclampsia (n = 68). Eighteen patients in this study required ventilatory support and the mean Glasgow coma scale was 12, indicating the severity of the condition of patients studied. The clinical characteristics of the 18 patients who had seizures following phenytoin were similar to those who did not have recurrent convulsions. No single clinical characteristic predicted recurrence of seizures. In all phenytoin ‘failures’ in this study, there were no focal neurological signs on admission and at a 6-week follow-up. The incidence of subsequent convulsions in eclamptic women receiving phenytoin was 26.5% which is considerably higher than the 10% reported by Sibai, in patients receiving MgSO, [4]. We conclude that seizure recurrence following phenytoin therapy in eclampsia is unacceptably high. The poor performance of phenytoin as an anticonvulsant in eclampsia may be due to severe cerebral vasospasm resulting in inadequate phenytoin levels in the brain to effect its anticonvulsant activity. An effective cerebral vasodilator may be a better choice for seizure prevention in eclampsia than a drug that primarily suppresses seizure foci. The results of this descriptive study add to the evidence of the large randomized clinical trial performed by the Eclampsia Trial Collaborative Group, comparing the safety and efficacy of these drugs in a homogeneous group of women with eclampsia. References
111 Eclampsia Trial Collaborative Group. Which anticonvulsant for women with eclampsia? Evidence from the Collaborative Eclampsia Trial. Lancet 1995; 345: 1455-1463. El Lucas MI, Levine KJ, Cunningham FG. A comparison of magnesium sulphate with phenytoin for the prevention of eclampsia. N Engl J Med 1995; 333: 201-205. [31 Moodley J, Naicker RS, Mankowitz E. Eclampsia - a methodof management. S Afr Med J 1983; 63: 530-535. [41 Sibai BM. Magnesium sulphate is the ideal anticonvulsant in pre-eclampsia-eclampsia. Am J Obstet Gynecol 1990; 162: 1141-1145.