Magnesium
Last updated 21st March 2019 - Tom Heaton
Function
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:
It’s actions can be seen by the effects that occur on administration.
This includes:
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
- Oxidative phosphorylation
- Glucose utilisation
- Protein synthesis
It’s actions can be seen by the effects that occur on administration.
This includes:
- CVS
- Antiarrhythmic properties
- Reduced vascular tone - peripheral, pulmonary, coronary
- Reduced response to vasoconstrictors
- Reduced catecholamine release (from adrenal medulla and adrenergic synapses)
- Direct myocardial depression (high levels)
- Antiarrhythmic properties
- Resp
- Bronchodilation
- Bronchodilation
- CNS
- Decreased ACh release at NMJ (through calcium antagonism)
- Decreased neuronal excitability
- Muscle weakness (high doses)
- Decreased ACh release at NMJ (through calcium antagonism)
- Metabolic
- Needed for thiamine metabolism
- Needed for thiamine metabolism
- Blood
- Inhibits platelet action
- Inhibits platelet action
Homeostasis
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.
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.
Therapeutic Use
Magnesium, as magnesium sulphate, has a number of clinical roles, some with more clinical evidence than others.
These include:
These include:
- Treating hypomagnesaemia
- Preeclampsia/eclampsia
- Asthma
- Arrhythmias
- Torsades De Pointes
- Atrial fibrillation
- Digitalis induced arrhythmias
- Torsades De Pointes
- Subarachnoid haemorrhage
- Pain
Preeclampsia
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.
Reduces risk of eclampsia.
Aim is for a supranormal level (2-4mmol/L).
Regime is usually 4g loading then 1g/hr with careful monitoring.
Arrythmias
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.
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.
Asthma
Theoretical bronchodilation through smooth muscle relaxation, reduction in histamine release and ACh release reduction.
True efficacy more controversial.
See the 3Mg trial: https://www.thebottomline.org.uk/summaries/icm/3mg/
True efficacy more controversial.
See the 3Mg trial: https://www.thebottomline.org.uk/summaries/icm/3mg/
Subarachnoid Haemorrhage
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.
The MASH-2 study seemed to demonstrate no real benefit.
Approach in now more commonly to maintain normal levels.
Pain
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.
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.
Administration
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.
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.
- Parikh, M. Webb, S. Cations: Potassium, calcium and magnesium. CEACCP. 2012. 12(4):195-198. https://academic.oup.com/bjaed/article/12/4/195/275340
- Nickson, C. Magnesium. LITFL. 2012. https://lifeinthefastlane.com/ccc/magnesium/
- Yu, A. Evaluation and treatment of hypomagnesemia. UpToDate. 2017.
- Yu, A. Regulation of magnesium balance. UpToDate. 2017.
- Lyness, D. Magnesium. Propofology. 2016. https://www.propofology.com/infographs/magnesium-uses-pharmacology-doses-cautions
- Yartsev, A. Hypermagnesemia. DerangedPhysiology. 2016. https://derangedphysiology.com/main/required-reading/electrolytes-and-fluids/Chapter%208.4.2/hypermagnesemia
- Yu, A. Gupta, A. Causes and treatment of hypermagnesemia. UpToDate. 2019.
- Yu, A. Gupta, A. Symptoms of hypermagnesemia. UpToDate. 2017.
