Magnesium sulfate pharmacology for maternal and critical-care indications: mechanisms, pharmacokinetics, and the therapeutic window

Hypertensive disorders of pregnancy and related critical illnesses remain leading global causes of maternal and perinatal morbidity, and magnesium sulfate is now a cornerstone therapy across obstetric, perinatal, and critical-care settings. However, its use in practice remains heterogeneous. This narrative, practice-oriented review synthesizes mechanistic, pharmacologic, clinical, and implementation evidence on magnesium sulfate use in pregnancy and critical illness. We draw on mechanistic and pharmacokinetic studies, randomized and observational clinical research, guidelines, and quality-improvement reports, emphasizing literature from 2020 to 2025 and selectively incorporating earlier landmark trials and classic pharmacology papers. We describe the multi-mechanistic actions that underpin anticonvulsant and neuroprotective effects, summarize pharmacokinetic variability and exposure targets, and appraise efficacy and safety across key indications, including prevention and treatment of eclampsia and severe preeclampsia, antenatal neuroprotection before very preterm birth, treatment of acute severe hypertension, and perioperative or critical-care adjunct use. We highlight how renal function, body size, and co-administered sedative or neuromuscular blocking agents shape dosing, toxicity risk, and monitoring strategies, and we contrast clinical examination-led and laboratory-led approaches to safety surveillance. At the systems level, we synthesize evidence on digital order sets, early-warning tools, remote postpartum blood pressure monitoring, and equity-stratified quality bundles designed to close gaps in timely treatment and safe monitoring, particularly in low-resource settings. Remaining gaps include precision dosing in special populations, long-term outcomes after antenatal exposure, and formal economic evaluations of care bundles that incorporate magnesium sulfate. Collectively, this review reframes magnesium sulfate as part of an integrated maternal and critical-care safety bundle and proposes a research agenda that links pharmacology, clinical trials, and implementation science to safer and more equitable use.