Nutrients, Vol. 18, Pages 1359: Magnesium in Neurocritical Care: Clinical Relevance, Status Assessment, and Practical Implications for Outcomes—A Narrative Review

Nutrients, Vol. 18, Pages 1359: Magnesium in Neurocritical Care: Clinical Relevance, Status Assessment, and Practical Implications for Outcomes—A Narrative Review

Nutrients doi: 10.3390/nu18091359

Authors:
Stefano Marelli
Lorenzo Querci
Arturo Chieregato

Background: Magnesium regulates neuronal excitability, NMDA receptor activity, and cerebrovascular tone. Dysmagnesemia is common in patients with acute brain injury (>65%), yet large randomized trials of magnesium neuroprotection have been neutral despite strong physiological rationale and consistent observational associations with outcomes. A key limitation may be diagnostic misclassification: the total serum magnesium poorly reflects the biologically active ionized fraction and may misclassify magnesium status in 20–85% of ICU patients during critical illness. Purpose: This narrative review synthesizes current evidence on magnesium physiology, measurement limitations, and clinical implications in neurocritical care. Overview: We discuss the mechanisms of magnesium depletion, outline the conceptual “two-hit” model (chronic deficiency plus acute ICU losses), and highlight the potential value of ionized magnesium for improved patient evaluation. Emerging syndrome-specific data suggest that magnesium disturbances are associated with prognostic signals. Improved phenotyping may help explain prior trial neutrality and support stratified approaches to magnesium monitoring and repletion. Future studies should evaluate magnesium-guided strategies and phenotype-driven trials to clarify the therapeutic role of magnesium in neurocritical care.

​Background: Magnesium regulates neuronal excitability, NMDA receptor activity, and cerebrovascular tone. Dysmagnesemia is common in patients with acute brain injury (>65%), yet large randomized trials of magnesium neuroprotection have been neutral despite strong physiological rationale and consistent observational associations with outcomes. A key limitation may be diagnostic misclassification: the total serum magnesium poorly reflects the biologically active ionized fraction and may misclassify magnesium status in 20–85% of ICU patients during critical illness. Purpose: This narrative review synthesizes current evidence on magnesium physiology, measurement limitations, and clinical implications in neurocritical care. Overview: We discuss the mechanisms of magnesium depletion, outline the conceptual “two-hit” model (chronic deficiency plus acute ICU losses), and highlight the potential value of ionized magnesium for improved patient evaluation. Emerging syndrome-specific data suggest that magnesium disturbances are associated with prognostic signals. Improved phenotyping may help explain prior trial neutrality and support stratified approaches to magnesium monitoring and repletion. Future studies should evaluate magnesium-guided strategies and phenotype-driven trials to clarify the therapeutic role of magnesium in neurocritical care. Read More

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