Background: Critical illnesses imply vital organ dysfunctions with high risk of imminent death. Magnesium is a bioessential element with multiple physiological effects relevant for vital body functions. It stabilizes excitable membranes contributing to proper neuromuscular, cardiovascular and respiratory functions. Ionized Mg2+ (iMg2+) is free bioactive form of Mg2+ in body fluids. Magnesium disorders in critically ill patients are often overlooked. Chronic Mg2+ deficiency is a condition of growing incidence in the general population and a significant factor in overall morbidity and mortality in critical illness. Main goal of this study was to investigate the existing literature related to determination of iMg2+ in the critically ill and to raise awareness of the problem of chronic Mg2+ deficiency in these patients. Methods: Search was conducted across electronic PubMed library database from 1975 to November 2024 using keywords concerning iMg2+ and critical care patients, to identify studies investigating the measuring of blood concentration of iMg2+ fraction in patients with critical health conditions. Search was limited to English language. Selection criteria included only studies on human, and excluded studies on animal population. Results: We identified 95 relevant studies. Reviewed papers show that abnormalities of Mg2+ levels are prevalent in critical illnesses. Their severity can impose vital threat. Disconcordance between total Mg2+ (tMg2+) and iMg2+ blood levels is frequently present in critical patients. Conclusions: Appropriate electrolyte analyzer assay is needed to promptly determine iMg2+ levels to assess Mg2+ status in critically ill patients, in order to help detect and correct Mg2+ imbalances and estimate the requirement for Mg2+ recompense in the case of deficiency, and thereby provide better outcome of the disease.

Magnesium is a bioessential mineral with multiple neuroactive effects. Mg2+ ion stabilizes excitable membranes. Epilepsy is the third most frequent chronic neurological condition characterized by spontaneous reappearance of unprovoked epileptic seizures, whose underlying mechanisms are not completely understood yet. A literature review on the role of magnesium in basic and clinical epileptology has been made in order to enlighten the importance of magnesium deficiency in the mechanisms of epileptic brain hyperexcitability, as well as the significance of including magnesium into the management of epilepsy patients. Neuronal magnesium requirements are high. The concentration of magnesium in the cerebrospinal fluid (CSF) is even higher than in the blood. In experimental epilepsy research, perfusing hippocampal slices with artificial CSF containing low concentration of extracellular Mg2+ is a frequently used animal model of spontaneously induced epileptiform activity. Magnesium deficiency is the most frequent clinically unrecognized electrolyte disbalance, often overlooked in epilepsy patients. Serum and CSF Mg2+ concentrations are lower in patients with epilepsy, as compared to healthy controls. Hypomagnesaemia increases seizure frequency and the risk of sudden unexpected death in pharmacoresistant epilepsy. Oral magnesium supplements help achieve better seizure control. Parenterally administered Mg2+ efficiently controls seizures in several epileptic encephalopathies in adults and children (in eclampsia, uremia, porphyria, febrile seizures, infantile spasms), and also helps control status epilepticus. Subclinical magnesium deficiency, very frequent in general population, acts as a factor contributing to seizure generation in epilepsy. It is recommended to assess magnesium status in epilepsy patients. This literature review reveals the therapeutic potential of magnesium as a simple antiepileptic agent, which exceeds its current clinical use.

Malikeh Ehghaghi, Marija Stanojevic, Ali Akram, Jekaterina Novikova. Proceedings of the 5th Clinical Natural Language Processing Workshop. 2023.

Magnesium ions regulate synaptic and nonsynaptic neuronal excitability from intracellular (Mg²⁺_i) and extracellular (Mg²⁺_o) domains, modulating voltage- and ligand-gated ion channels. K+ inward rectifier (Kir) channel inward rectification arises from Mg²⁺_i blocking the pore and outward K⁺ current, while Mg²⁺_o targets external sites. Mg²⁺_i causes voltage-dependent Ca²⁺ voltage-gated (Ca_V) and Na⁺ voltage-gated (Na_V) channel block while phosphorylation modulates channel activity. Mg²⁺_o elicits direct voltage-dependent Ca_V channel block, and screens surface charge, and in Na_V channels reduces conduction and may cause depolarization by quantum tunneling across closed channels. Mg²⁺_i is an allosteric large conductance Ca²⁺-activated K⁺ (BK) channel activator, binding to low-affinity sites to alter Ca²⁺ and voltage sensitivity but reduces small conductance Ca²⁺-activated K⁺ (SK) channels’ outward K⁺ current and induces inward rectification. N-Methyl-D-aspartate receptor (NMDAR) channels are inhibited by Mg²⁺_i binding within the pore, while Mg²⁺_o stabilizes excitability through voltage-dependent block, Mg²⁺_o forms Mg-ATP complex modifying purinergic P2X receptor (P2XR) channel affinity and gating and directly blocks the pore. Mg²⁺_o reduces gamma-aminobutyric acid type A receptor (GABA_AR) channel Cl⁻ current amplitude and augments susceptibility to blockers. Mg²⁺_o and Mg²⁺_i block nicotinic acetylcholine receptor (nAChR) channels through voltage-dependent pore binding and surface charge screening, impeding current flow and altering gating.