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

**Authors:** Mingya Xia, Qiang Ni, Sha Zhu

PMC · DOI: 10.3389/fphar.2026.1749828 · Frontiers in Pharmacology · 2026-02-20

## TL;DR

This paper reviews how magnesium sulfate is used in pregnancy and critical care, focusing on its mechanisms, dosing, and safety to improve maternal and fetal outcomes.

## Contribution

The paper synthesizes recent evidence on magnesium sulfate pharmacology and implementation strategies to guide safer and more equitable clinical use.

## Key findings

- Magnesium sulfate's anticonvulsant and neuroprotective effects are supported by multiple mechanisms.
- Pharmacokinetic variability and dosing adjustments are influenced by renal function and co-administered drugs.
- Digital tools and quality bundles can improve magnesium sulfate safety and access in low-resource settings.

## Abstract

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.

## Linked entities

- **Chemicals:** magnesium sulfate (PubChem CID 24083)
- **Diseases:** eclampsia (MONDO:0001754), severe preeclampsia (MONDO:0001641)

## Full-text entities

- **Genes:** CALM1 (calmodulin 1) [NCBI Gene 801] {aka CALML2, CAM2, CAM3, CAMB, CAMC, CAMI}, Prdx6 (peroxiredoxin 6) [NCBI Gene 94167] {aka LPCAT-5}, NMB (neuromedin B) [NCBI Gene 4828], Nfe2l2 (NFE2 like bZIP transcription factor 2) [NCBI Gene 83619], Mapk14 (mitogen activated protein kinase 14) [NCBI Gene 81649] {aka CRK1, CSBP, CSPB1, Csbp1, Csbp2, Exip}, ICAM1 (intercellular adhesion molecule 1) [NCBI Gene 3383] {aka BB2, CD54, P3.58}, MYLK (myosin light chain kinase) [NCBI Gene 4638] {aka AAT7, KRP, MLCK, MLCK1, MLCK108, MLCK210}, IL12B (interleukin 12B) [NCBI Gene 3593] {aka CLMF, CLMF2, IL-12B, IMD28, IMD29, NKSF}, CXCL8 (C-X-C motif chemokine ligand 8) [NCBI Gene 3576] {aka GCP-1, GCP1, IL8, LECT, LUCT, LYNAP}, NFKB1 (nuclear factor kappa B subunit 1) [NCBI Gene 4790] {aka CVID12, EBP-1, KBF1, NF-kB, NF-kB1, NF-kappa-B1}, IL1B (interleukin 1 beta) [NCBI Gene 3553] {aka IL-1, IL1-BETA, IL1F2, IL1beta}, Ifng (interferon gamma) [NCBI Gene 25712] {aka IFNG2, If2f}, ALB (albumin) [NCBI Gene 213] {aka FDAHT, HSA, PRO0883, PRO0903, PRO1341}, TNF (tumor necrosis factor) [NCBI Gene 7124] {aka DIF, IMD127, TNF-alpha, TNFA, TNFSF2, TNLG1F}, Tnf (tumor necrosis factor) [NCBI Gene 24835] {aka RATTNF, TNF-alpha, Tnfa}, Il1b (interleukin 1 beta) [NCBI Gene 24494] {aka IL-1F2}, IL6 (interleukin 6) [NCBI Gene 3569] {aka BSF-2, BSF2, CDF, HGF, HSF, IFN-beta-2}
- **Diseases:** sepsis (MESH:D018805), neuromuscular blockade (MESH:D020879), bradycardia (MESH:D001919), hemolysis (MESH:D006461), SMM (MESH:D045169), hypoxia (MESH:D000860), vomiting (MESH:D014839), placental abruption (MESH:D000037), analgesia (MESH:D000699), preeclamptic (MESH:C538543), posterior reversible encephalopathy syndrome (MESH:D054038), pregnancy (MESH:D011254), NMBs (MESH:D009468), hypotension (MESH:D007022), placental ischemia (MESH:D007511), preterm labor (MESH:D007752), seizure (MESH:D012640), PPROM (MESH:C563032), MIPD (MESH:D004195), acute kidney injury (MESH:D058186), postpartum hemorrhage (MESH:D006473), stroke (MESH:D020521), involuntary-movement (MESH:D020820), paralysis (MESH:D010243), chronic lung disease (MESH:D029424), fatigue (MESH:D005221), maternal morbidity (MESH:D063130), block (MESH:D006327), organ dysfunction (MESH:D009102), intraventricular hemorrhage (MESH:D000074042), nausea (MESH:D009325), neuromuscular block (MESH:D055191), obesity (MESH:D009765), depression (MESH:D003866), Renal impairment (MESH:D007674), neuromuscular or respiratory compromise (MESH:D012131), PONV (MESH:D020250), edema (MESH:D004487), chronic kidney disease (MESH:D051436), obstetric hemorrhage (MESH:D048949), asthma (MESH:D001249), dizziness (MESH:D004244), neuroinflammation (MESH:D000090862), blood loss (MESH:D016063), atrioventricular block (MESH:D054537), Pre-eclampsia (MESH:D011225), cardiac arrest (MESH:D006323), pulmonary edema (MESH:D011654), bronchopulmonary dysplasia (MESH:D001997), Toxicity (MESH:D064420), lethargy (MESH:D053609), prelabor rupture of membranes (MESH:D005322), HELLP (MESH:D017359), Eclampsia (MESH:D004461), renal failure (MESH:D051437), agitation (MESH:D011595), preterm birth (MESH:D047928), HDP (MESH:D046110), PD (MESH:D010300), intracerebral hemorrhage (MESH:D002543)
- **Chemicals:** calcium (MESH:D002118), dextrose (MESH:D005947), creatinine (MESH:D003404), remifentanil (MESH:D000077208), magnesium (MESH:D008274), nitric oxide (MESH:D009569), glutamate (MESH:D018698), propofol (MESH:D015742), N-methyl-D-aspartate (MESH:D016202), ACh (MESH:D000109), prostaglandin E2 (MESH:D015232), lipopolysaccharide (MESH:D008070), diazepam (MESH:D003975), labetalol (MESH:D007741), nicardipine (MESH:D009529), calcium gluconate (MESH:D002125), nifedipine (MESH:D009543), voltage (MESH:C069547), Magnesium Sulphate (MESH:D008278), hydralazine (MESH:D006830), nitroglycerin (MESH:D005996), Dexmedetomidine (MESH:D020927), furosemide (MESH:D005665), phenytoin (MESH:D010672), oxygen (MESH:D010100), MAGENTA (MESH:D012394), rocuronium (MESH:D000077123), midazolam (MESH:D008874), benzodiazepines (MESH:D001569), urapidil (MESH:C015568), lidocaine (MESH:D008012), Ca2+ (-)
- **Species:** Homo sapiens (human, species) [taxon 9606], Rattus norvegicus (brown rat, species) [taxon 10116]

## Full text

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## Figures

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## References

87 references — full list in the complete paper: https://tomesphere.com/paper/PMC12963761/full.md

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Source: https://tomesphere.com/paper/PMC12963761