Magnesium is one of the major cations of the body. It is the fourth most abundant (after sodium, potassium and calcium). It is primarily intracellular and and mainly stored within bone.
It can be considered as being the physiological antagonist of calcium. It interacts with a number of important physiological systems including:
ATP synthesis and action
Na+/K+ ATPase system
Adenylyl cyclase cAMP
It’s actions can be seen by the effects that occur on administration. This includes:
Reduced vascular tone - peripheral, pulmonary, coronary
Reduced response to vasoconstrictors
Reduced catecholamine release (from adrenal medulla and adrenergic synapses)
Direct myocardial depression (high levels)
Decreased ACh release at NMJ (through calcium antagonism)
Decreased neuronal excitability
Muscle weakness (high doses)
Needed for thiamine metabolism
Inhibits platelet action
The normal plasma level of magnesium is 0.7-1.0 mmol/L. In the plasma it exists in the ionised and unionised form, of which it is the ionised that has activity. Throughout the body it primarily exists intracellularly (second most important intracellular cation after K+) in muscle and soft tissue, and in bone. There is usually no net change in levels, with loss being balanced by input.
Intake is from the gut from dietary sources, usually about 360mg/day. There is a balance of absorption (small bowel and large bowel) but also some excretion in intestinal secretions (about 40mg/day). Calcium and magnesium absorption are interrelated, and part of the reason for the frequent joint deficiency that is seen.
Excretion of magnesium occurs from the kidney, where the handling is a little different from most other ions. It is freely filtered at the glomerulus (about 80%) but is primarily reabsorbed at the thick ascending limb of the loop of Henle. An important driving force is the electrochemical gradient from the Na-K-2Cl cotransporter, with paracellular movement of magnesium.
Unlike many of the other ions, magnesium doesn’t really have a significant hormonal regulator. The plasma magnesium level itself seems to be a direct physiological regulator of magnesium reabsorption in the loop of Henle. Metabolic acidosis, hypokalaemia and hypophosphataemia also lead to reduced magnesium reabsorption from the loop of Henle. There are some mild effects from hormones on magnesium handling. Parathyroid hormone acts to increase gut absorption and reduce renal excretion. Aldosterone acts to increase renal excretion. There is little interaction with bone stores for all these mechanisms (in the short term), so plasma levels are primarily dependent on the balance of input and output on the non-bone stores. In the face of acute drops, the processes above primarily work to reduce normal renal losses. Renal losses can be reduced to under 5 mmol/day. More chronically there may be some mobilisation of bone stores.
Magnesium, as magnesium sulphate, has a number of clinical roles, some with more clinical evidence than others. These include:
Torsades De Pointes
Digitalis induced arrhythmias
Fairly well established benefit here. Reduces risk of eclampsia. Aim is for a supranormal level (2-4mmol/L). Regime is usually 4g loading then 1g/hr with careful monitoring.
Would appear to be beneficial in cases where there is hypomagnesaemia. This may also include when total body magnesium deficiency which may be hard to assess. Recommended for the treatment of Torsades De Pointes (TDP). Some use in treatment of critical illness AF.
Previous research had suggested benefit from an anti-vasospasm effect. The MASH-2 study seemed to demonstrate no real benefit. Approach in now more commonly to maintain normal levels.
Magnesium may have an adjunctive role in perioperative pain management. It is an antagonist at the NMDA receptor and so may interfere with wind-up pathways. There is some clinical evidence of a reduction in perioperative morphine requirements when used as an adjunct.
The route will generally be IV in cases of symptoms, and orally if asymptomatic. It is generally benign, with toxicity being exerted at notably higher than normal levels. Rapid IV administration can lead to hypotension though. 1g of magnesium sulphate is equivalent to 4 mmol of magnesium ions.
Concomitant correction of other electrolyte abnormalities (Potassium, calcium) is often also needed.
Links & References
Watson, V. Vaughan, R. Magnesium and the anaesthetist. CEPD Review. 2001.