Low Dose Magnesium Sulphate Versus Standard Pritchard Regimen In Management Of Severe Preeclampsia/Eclampsia: A Randomised Controlled Trial

Introduction Preeclampsia complicates 5-7% of all pregnancies globally. However, hospital-based studies in Nigeria have reported rates ranging between 1.2% and 6.3%, while a study in Abakaliki recorded 0.99% for severe preeclampsia and 0.76% for eclampsia. Severe preeclampsia and eclampsia are associated with increased maternal and perinatal morbidity and mortality. The World Health Organization (WHO) estimates that about 63,000 maternal deaths occur annually from preeclampsia/eclampsia and associated complications, with 98% of these deaths occurring in developing countries. Perinatal adverse outcomes are usually due to prematurity associated with preterm delivery, as well as intrauterine fetal death from intrauterine growth restriction and placental abruption. Early recognition therefore, combined with prompt management, is often required for good maternal and perinatal outcome.

The definitive treatment for severe preeclampsia or eclampsia is delivery of the placenta. In affected women, positive maternal and perinatal outcomes depend on the woman having timely access to a treatment package which include effective inpatient monitoring, optimal timing of childbirth, presence of skilled attendant at birth and administration of antihypertensive as well as anticonvulsive therapy. Of all the anticonvulsants that have been tried in the management of preeclampsia and eclampsia, magnesium sulphate (MgSO4) has been established as the anticonvulsant of choice both for prevention of convulsions in severe preeclampsia and for prevention of recurrent convulsions in eclampsia. It has been shown to be superior to diazepam, phenytoin, and lytic cocktail (a mixture of chlorpromazine, promethazine and pethidine) in reducing the occurrence of eclamptic convulsion and the associated maternal morbidity and mortality. It also has beneficial effects on fetuses, reducing the risks of low Apgar scores in the 1st and 5th minutes, the risk of cerebral haemorrhage, as well as the need for intubation and admission into newborn intensive care units.

Magnesium sulphate belongs to the class of electrolytes anti-dysrrhythmic drugs. It is a sterile, non-pyrogenic concentrated solution of magnesium sulphate heptahydrate in water for injection. It is administered by the intravenous (IV) or intramuscular (IM) routes as an electrolyte replenisher or anticonvulsant. It has been adjudged to be the most effective, safe and low-cost anticonvulsant drug for pre-eclampsia and eclampsia. Though the mechanism of action is not completely understood, several hypotheses have been put forward to explain its beneficial effects in patients with preeclampsia and eclampsia. These include dilatation of cerebral blood vessels thereby reducing cerebral ischaemia, blockade of the N-methyl-D-aspartate receptors in the brain and also causing peripheral vasodilatation. However, despite its endorsement by the W.H.O. and its widespread availability, MgSO4 is still underused and incorrectly administered in many low resource settings. This has been discovered to be due to a number of provider factors and the complexity of treatment regimens being used.

The most commonly used MgSO4 regimens are those given intramuscularly and/or intravenously from the diagnosis of severe preeclampsia and eclampsia to 24 hours post delivery or post last seizure episode, whichever occurs later. Though these regimens have been found to be effective, they involve administering large doses of the drug. This usually leads to high cost of treatment to the affected patients as well as difficulties in monitoring such patients for drug toxicity (which include neurological deficit and cardiac arrest), especially in developing countries where manpower and facilities are limited. Therefore, several attempts have been made either to shorten the duration of administration or reduce the dosage of MgSO4 with the aim of achieving optimal efficacy, while reducing the side effects of the drug and the cost of management. These include those in which the loading dose and maintenance doses were reduced in quantities; those involving reduction of maintenance dose to 12 hours and those involving giving only the loading dose. No particular regimen has been generally adopted as the minimum effective dose, although several lower doses have proved to be effective. Because of their effectiveness which has been demonstrated over time, it has been suggested that lower doses of MgSO4 may suffice for prophylaxis for patients with severe preeclampsia as well as treatment for those with eclampsia, without jeopardising efficacy.

Though the reason for the success recorded with the low dose regimen used in Dhaka was attributed to the low body mass index of the population, several other studies in other places with varying dosages and different weight distribution have also recorded varying degrees of success. Therefore small body mass index (BMI) alone may not be enough to explain the whole phenomenon. Some authorities have also shown that there is no association between treatment failures and patients' BMI. or with serum magnesium levels. A systematic review in Nigeria in 2016 supported the fact that there were no studies that had demonstrated the lowest effective dose of MgSO4 to manage preeclampsia/eclampsia. Another systematic review also recommended further studies to identify the minimum effective dose of MgSO4 for the management of preeclampsia/eclampsia. Therefore, any regimen that will involve minimal cost and side effects; and at the same time be as effective as the current doses being administered, will go a long way in reducing the challenges of affordability of the drug and that of its side effects. It is against this background that this study is being carried out to compare the efficacy of a lower dose of MgSO4 in patients with severe pre-eclampsia and eclampsia to that of the Pritchard's regimen among our women population with a view to recommending it for use if the efficacy is found to be comparable.