A comprehensive literature search was conducted across the following electronic databases: PubMed, Scopus, Cochrane Library, ProQuest, and ScienceDirect, from inception until April 18, 2025. The search aimed to identify studies evaluating the use of MgSO ₄ in neuroanesthesia and neurocritical care settings. Search strategies were customized for each database using a combination of Medical Subject Headings (MeSH), controlled vocabulary, and free-text terms. Boolean operators (AND, OR) and advanced search filters were applied to optimize sensitivity and specificity of the results. The detailed search strategy for each database is presented in Table 1.

Studies were included if they met the following criteria: (1) observational studies; (2) adult patients undergoing neurosurgical procedures or managed in a neurocritical care setting; (3) interventions involving the administration of intravenous or intracisternal MgSO ₄ in any dosage, timing, or duration; (4) comparator group receiving either placebo or standard care; and (5) reporting at least one relevant clinical outcome, such as neurological recovery (e.g., modified Rankin Scale or Glasgow Outcome Scale), occurrence of cerebral vasospasm or delayed cerebral ischemia, intraoperative anesthetic or opioid requirements, hemodynamic parameters, pain scores, or adverse events. Studies were excluded if they were non-randomized (e.g., observational studies, case reports, case series), involved pediatric or animal populations, lacked complete outcome data, were not conducted in neuroanesthesia or neurocritical care contexts, or were not available in English.

Two independent reviewers screened all titles and abstracts for eligibility. Full-text articles of potentially relevant studies were assessed in detail. Discrepancies in study selection or data interpretation were resolved through discussion, with input from a third reviewer when necessary. From each included study, we extracted data on the first author and publication year, study design, country of origin, clinical setting, patient population, MgSO ₄ regimen (including dose, route of administration, timing, and duration), comparator treatment, and all reported outcomes relevant to this review.

The methodological quality of the included RCTs was assessed using the Cochrane Risk of Bias 2.0 tool. This tool evaluates bias across five domains: randomization process, deviations from intended interventions, missing outcome data, measurement of outcomes, and selection of reported results. Each study was rated as having a low risk of bias, some concerns, or a high risk of bias. Moreover, case control or series were assessed using the Newcastle-Ottawa Scale (NOS) criteria. All assessments were performed independently by two reviewers, and any disagreements were resolved by consensus.

Our comprehensive literature search on 5 international databases resulted in 569 identifiable articles, from which 57 studies were removed as duplicate. Furthermore, from 512 studies screened by title, 427 record were excluded due to inadequate similarity with our inclusion and exclusion criteria. Subsequently, 85 studies were screened by abstract and 72 studies were excluded. Finally, 3 studies were excluded as the full-text version is unavailable. In total, 10 studies were included in our systematic review. The detailed flow of literature search according to the PRISMA guideline is shown in Figure 1.

Ten included studies in this systematic review consisted of 8 RCTs and 2 case reports conducted in diverse neurosurgical and neurocritical care settings. The trials ranged from 2010 to 2024 and were conducted in both high-income and middle-income countries, including Germany, Japan, South Korea, India, and the United States. Participants across studies were adult patients undergoing various neurosurgical procedures such as aneurysm clipping, craniotomy, and spine surgery, or those being treated for subarachnoid hemorrhage or acute ischemic stroke in neurocritical care units.

The intervention across all trials was the administration of MgSO ₄ via intravenous or intracisternal routes, with variation in dosage and duration. Comparators included placebo (e.g., saline), standard care, or in some cases, no treatment. Primary outcomes assessed included neurological recovery measured by the modified Rankin Scale (mRS), incidence of cerebral vasospasm and delayed cerebral ischemia (DCI), intraoperative anesthetic and opioid requirements, pain scores, intraoperative hemodynamic stability, and occurrence of adverse events. The detailed characteristics of each studies can be seen in Table 2.

Most included RCTs had a low risk of bias across key domains, including randomization, intervention adherence, and outcome reporting (See extended data ³⁶ ). Trials by Sohn et al. (2021), Bechler et al. (2020), and others demonstrated strong methodological quality with minimal limitations. Two case-control studies (Feulner et al., 2024; Choudhary et al., 2021) were rated as high quality using the Newcastle-Ottawa Scale. These findings support the overall reliability of the review.

The anti-inflammatory properties of magnesium sulfate (MgSO ₄) were evaluated by Etezadi et al in a randomized controlled trial involving patients undergoing elective craniotomy. Although C-reactive protein levels did not differ significantly between groups (p = 0.243), patients receiving MgSO ₄ had significantly lower mean arterial pressure (I: 71.3 ± 4.3 vs. C: 84.5 ± 5.6 mmHg; p = 0.03), improved hemodynamic stability, and reduced intraoperative anesthetic requirements. These findings suggest that magnesium may mitigate surgical stress and systemic inflammation, contributing to neuroprotection through reduced neuronal excitotoxicity and enhanced perfusion.

Several trials examined the effect of MgSO ₄ on neurological recovery using the modified Rankin Scale (mRS). Feulner et al ¹⁵ found improved long-term functional outcomes in patients treated with magnesium following microsurgical or endovascular intervention for ruptured cerebral aneurysms, with more patients achieving favorable mRS scores (0–3) in the intervention group (22 vs. 15). Similarly, Takeuchi et al ¹⁸ reported that 67% of patients receiving intracisternal MgSO ₄ achieved good outcomes (mRS 0–2) at one year, compared to 23% in the control group (p = 0.019). Furthermore, the combination of magnesium with hydrogen therapy (Mg+H ₂) showed an even higher proportion of favorable recovery (75%). However, findings from larger multicenter trials were mixed. However, Wong et al ²² Wong et al. reported no significant difference in favorable mRS outcomes at six months between magnesium and control groups (64% vs. 63%; OR 1.0, 95% CI 0.7–1.6), suggesting that benefits may depend on patient selection, timing, and method of administration. Likewise, Saver et al ²⁰ and Shkirkova et al ¹⁹ found no difference in 90-day mRS scores (both 2.7; p = 1.00) or mortality (15.4% vs. 15.5%; p = 0.95) among acute stroke patients, indicating limited efficacy of MgSO ₄ when administered later or in less targeted populations.

Magnesium sulfate demonstrated significant benefits in reducing the incidence of cerebral vasospasm and delayed cerebral ischemia. In Feulner et al.’s study, patients receiving MgSO ₄ had a lower incidence of angiographic vasospasm (33% vs. 46%) and DCI (13% vs. 42%), with early initiation and dose titration based on mean arterial pressure. ¹⁵ These findings were further supported by Takeuchi et al., who reported a dramatic reduction in vasospasm (8% vs. 62%; p = 0.014) and DCI (8% vs. 54%; p = 0.023) in the magnesium group compared to controls. Notably, the Mg+H ₂ combination group also showed a substantial benefit, indicating a synergistic neurovascular protective effect. ¹⁸

The analgesic benefits of magnesium were highlighted in a randomized controlled trial by Sohn et al., which included 72 patients undergoing major spine surgery. Patients in the magnesium group experienced significantly lower postoperative pain scores at both 24 hours (3.2 ± 1.7 vs. 4.4 ± 1.8; p = 0.009) and 48 hours (3.0 ± 1.2 vs. 3.8 ± 1.6; p = 0.018) compared to controls. Additionally, the magnesium group required more than 30% less fentanyl and had a reduced need for supplemental neuromuscular blockers, emphasizing magnesium’s dual analgesic and muscle-relaxant roles in perioperative care. ¹⁷

Choudhary et al ¹⁶ demonstrated that intraoperative magnesium infusion improved hemodynamic stability in patients undergoing intracranial aneurysm surgery. Patients treated with magnesium maintained more consistent blood pressure and heart rate, required lower doses of opioids, and experienced no postoperative complications such as nausea, vomiting, or shivering. These findings suggest that magnesium may enhance anesthetic depth and reduce perioperative drug requirements without compromising safety.

The safety profile of magnesium sulfate across studies remained reassuring. Bechler et al ³ reported that 14.1% of patients experienced at least one cardiac event, including atrial fibrillation, bradycardia, or cardiac arrest, with no statistically significant difference between the magnesium and placebo groups (p = 0.93). Similarly, Saver et al ²⁰ and Shkirkova et al ¹⁹ found no significant difference in the rates of serious adverse events or mortality, supporting the tolerability of MgSO ₄ even in high-risk neurocritical care settings. These consistent findings underscore the relative safety of magnesium administration in neurosurgical and stroke populations when used within therapeutic dosing limits.