Eclampsia is a known deleterious sequela of preeclampsia. It has been defined as new-onset generalized tonic-clonic seizures in patients with preeclampsia. Preeclampsia is the occurrence of hypertension [HTN] after 20 weeks of gestation with concurrent proteinuria/end-organ dysfunction [1]. Annually, both eclampsia and preeclampsia account for nearly 63,000 maternal deaths worldwide [2]. A study conducted by the Centers for Disease Control and Prevention [CDC] found an overall case-fatality rate of preeclampsia and eclampsia to be 6.4 per 10,000 cases at delivery. This study also found an increased risk of death in patients at 20-28 weeks of gestation and 3.1 times increased incidence of preeclampsia/eclampsia in black women compared to white women [3].
Eclamptic seizures are a medical emergency and can arise after 20 weeks of gestation, either antepartum, intrapartum, or postpartum. They require urgent intervention to prevent death in the mother and fetus [1]. Magnesium sulfate [MgSO4] has been proven to be an effective first-line treatment for the prevention and treatment of eclampsia [1,4]. It should be continued for at least 24 hours from the time of the last seizure and the patient should be monitored closely for toxicity [1]. Even with the risk of side effects and toxicity, many studies have proven that MgSO4 is much more superior in the treatment of eclampsia compared to other drugs [4,5]. Nevertheless, the prevalence of eclampsia has decreased because of enhanced prenatal care, judicious use of medical therapy [blood pressure control, seizure prophylaxis, etc.], and conducting term deliveries by either induction or cesarean section [6]. In this review, we discuss the mechanism of eclampsia, the pharmacokinetics and pharmacodynamics of MgSO4, the efficacy of MgSO4 in reducing mortality in eclamptic patients, and the challenges encountered in MgSO4 administration.
Pathophysiology of eclampsia
Although a comprehensive review of the pathophysiology is beyond the scope of this article, a brief mention of some of the key elements involved in the pathophysiology of eclampsia has been discussed. Eclampsia is a complication of preeclampsia, which is why it is important to understand the pathogenesis of preeclampsia. The placenta is considered to play a significant role in the pathophysiology of preeclampsia. After the placenta is delivered, the symptoms subside quickly [7]. The primary issue is that placental-derived factors released into the maternal circulation cause diffuse endothelial dysfunction, vasoconstriction, and increased vascular permeability, resulting in HTN, proteinuria, and edema [8].
The main pathophysiological occurrences can be understood in a simplified manner using the widely accepted “two-stage theory,” which states that preeclampsia develops in two stages. The first is decreased placental perfusion [Stage 1], which results in the release of factors that cause generalized systemic pathology [Stage 2] [9]. The rest of the pathophysiology is explained in Figure 1 [8-11].
According to studies, eclampsia is caused by both cerebral edema and vasospasm. Edema can be generalized or localized, such as in the occipital lobes, white matter, or watershed regions. Vasospasm has been observed in both angiographic and Doppler studies leading to ischemia, causing reduced perfusion of the brain. All of this culminates in edema and microinfarcts [and, on rare occasions, hemorrhage] in these patients [12-15]. Because cerebral edema develops within the restricted area of the skull, it causes progressive brain compression as well as the usual neurologic symptoms of eclampsia such as headache, nausea, vomiting, cortical blindness, and convulsions [16,17].
Pharmacokinetics and pharmacodynamics of magnesium sulfate
Regimens
MgSO4 is usually administered by either intramuscular [IM] or intravenous [IV] routes. The two standard regimens that are most commonly used for the management of severe preeclampsia and eclampsia are predominantly the IM Pritchard regimen and the exclusively IV Zuspan regimen [18]. The Pritchard regimen involves administering two loading doses of MgSO4, consisting of a slow IV dose of 4 g over five to ten minutes, immediately followed by an IM dose of 10 g divided into 5 g in each buttock. This is then followed by maintenance dosing with 5 g IM into the alternate buttocks every four hours [19]. In the Zuspan regimen, a single loading dose of 4 g is administered as a slow IV infusion over five to ten minutes, followed by an hourly maintenance infusion of 1-2 g by a controlled infusion pump [20]. The serum concentrations of magnesium obtained from the Pritchard regimen fluctuate more often compared to the Zuspan regimen [21].
Pharmacokinetics
After administration, about 40% of plasma magnesium becomes protein-bound, while the unbound ionized magnesium increases proportionately to the total serum concentration of magnesium [22]. The free magnesium ions diffuse into the extravascular space, into the bone, and across the placenta and fetal membranes to enter the fetus and amniotic fluid [23-25]. Magnesium is eliminated almost exclusively by the maternal kidneys, with almost 90% of the dose excreted in the urine during the first 24 hours after an IV infusion [26]. A plasma concentration of 1.8-3.0 mmol/L is recommended for the treatment of eclamptic seizures while carefully monitoring for toxicity beyond this recommended concentration. The first warning of imminent toxicity in the mother is the loss of the patellar reflex at concentrations between 3.5 and 5 mmol/L [26]. Respiratory paralysis and cardiac arrest may occur at supratherapeutic concentrations beyond 5 mmol/L [27]. Therefore, close monitoring for the loss of deep tendon reflexes, respiratory rate