Study design: This is Randomised Controlled Trial
(CTRI registration number: CTRI/2022/01/039776)
Study site: This study will be conducted at obstetric unit of JNMC (Jawaharlal Nehru Medical College) and AVBRH (Acharya Vinoba Bhave Rural Hospital), Sawangi, Wardha
Study duration: 2 years
Sample size: Assuming that the proportion of severe pre-eclamptic women experiencing seizure in both 12-hour and 24-hour arm to be 1%, inferiority margin of 5%, with a statistical power of 80% and a two-sided p value of 0.05, 49 women are needed per group. Considering loss to follow up of 10%, the final sample size resulted in a total of 54 women per group.
Final sample size: 108 (54 in each group)
Criteria for inclusion
1. Age of patient >=18 years.
2. Patients of severe preeclampsia based on:
- Increased blood pressures of 160/110mm Hg or more after 20 weeks of gestation on two different occasions at least 4 hours apart and
- Proteinuria of 3+ on dipstick or 5 gm in 24 hours urine sample
3. Singleton pregnancy
4. who give consent for participation in study
Criteria for exclusion
- Age of patient < 18 years
- Patients with either antepartum or intrapartum or postpartum convulsions(before enrollment)
- Patients with known case of epilepsy
- Patients with renal or liver disorder, not attributed to preeclampsia
- Central Nervous System disorder
- Chronic kidney disease
- Seizures due to metabolic disturbances, space occupying lesions or intra cerebral infections
- Cardiac patients
- Contraindications to MgSO4 i.e. drug hypersensitivity, myasthenia gravis, anuria or oliguria
- Prior intake of any other anticonvulsant
Statistical methods :Chisquare test and Student’s unpaired t test
Software’s Used in the study : SPSS 24.0 version, EPI-INFO 7.0 version and GraphPad Prism7.0 version.
All women admitted to the obstetric (ANC) ward of hospital with diagnosis of severe preclampsia, will be screened by on duty gynae doctor and if found eligible i.e. meeting inclusion and exclusion criteria, patient will be then enrolled in study. Diagnosis of severe preclampsia will be done on the basis of blood pressure more or equal to 160/110 mm Hg, measured on two different occasions, 4-6 hours apart, proteinuria of 3+ on dipstick or 5 gm in 24 hours urine sample, with one or more of the following features like epigastric pain or right upper quadrant pain, oliguria of less than 500ml/24 hour, impaired liver function, thrombocytopenia, fetal growth restriction, pulmonary edema or cyanosis, visual disturbances(6–8).
Patient information sheet will be given to patient and relative and informed consent will be taken and patient will be randomised to either short duration therapy or standard duration therapy (Figure 1). All required blood investigations like complete blood count, blood group, viral markers for HIV, HbsAg, VDRL, Sickling (if not done prior), coagulation profile including bedside bleeding time and clotting time(BT and CT), kidney function test (KFT) and liver function test (LFT) will be sent. Baseline serum magnesium levels will be measured and will be repeated after 4 hours of loading dose and 4 hours of completion of maintenance therapy.
All enrolled patients of study will receive loading dose of MgSO4, 4 gm intravenously. The dose will be constituted by diluting 8 mL of 50% MgSO4 solution with 12 mL of normal saline to obtain 20 mL of 20% 4gm MgSO4 which will be administered slowly over 15–20min. Maintenance dose will be given as 1gm/hour as continuous intravenous infusion with infusion pump. Patient randomized to 12hours therapy group will be given maintenance therapy for 12 hours, and those randomized to 24 hours therapy will be given maintenance therapy for 24 hours. In study group of 12 hours, if there is persistent severe hypertension/ appearance of signs or symptoms of impending convulsions, the maintenance dose will be continued for 24 hours. If any patients develops seizures during maintenance therapy or after completion of therapy then patients will be given 2 gm of 20% MgSO4 intravenously as a repeat loading dose and her maintenance dose will then be continued for 24 hours. If a patient develops second recurrent episode of convulsions during therapy then anticonvulsant medicine (phenytoin) will be started after discussion with physician. Patients developing seizures after 48-72 hours after delivery, will be evaluated for other causes of convulsions (17).
Clinical monitoring protocol:
During the entire duration of treatment, all patients will be in the high dependency unit (HDU) and will be monitored hourly for blood pressure, deep tendon reflexes (patellar reflex), urine output, respiratory rate and occurrence of seizures. Patients will be catheterised by Foleys catheter, and strict input and output charting will be done. Catheter will be retained till the last dose of magnesium sulphate. All details of magnesium sulphate treatment like timing, doses will be recorded, serum magnesium levels will be measured at baseline, after 4 hours of loading dose and 4 hours after cessation of therapy. Features of magnesium toxicity, if any will be noted. All patients will be followed up till discharge.
Apart from magnesium sulphate treatment, other management of study patients will be done as per institutional protocol, like antihypertensive medicine for raised blood pressure, decision on mode of delivery, induction of labour, fetal heart rate monitoring. Mode of delivery, duration of labour, maternal complications if any, will be recorded. All neonatal details like gestational age at delivery, baby weight at birth, APGAR score at 1 and 5 minutes, need of admission in neonatal intensive care unit (NICU) will be noted. After delivery all necessary postpartum care will be provided to patients and baby care will be done as per hospital protocol, till discharge.