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This channel may make reference to guidelines produced by a number of NHS organisations. The content on this channel reflects my professional interpretation/summary of the guidance and I am in no way affiliated with, employed by or funded/sponsored by them.

My name is Fernando Florido (also known as Juan Fernando Florido Santana), a GP in the UK. In this episode, I will go through the assessment and management of hypomagnasemia, focusing on what is relevant in Primary Care only. For this advice I have looked at the published guidance by NHS Dorset, NHS Kent and Medway, NHS Lanarkshire, Gloucestershire Hospitals NHS Trust, and Royal Cornwall Hospitals NHS Trust. The links to this guidance can be found below.

I am not giving medical advice; this video is intended for health care professionals, it is only my summary and my interpretation of the guidelines and you must use your clinical judgement.  

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There is a podcast version of this and other videos that you can access here:

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There is a YouTube version of this and other videos that you can access here: 

• The Practical GP YouTube Channel: 

https://youtube.com/@practicalgp?si=ecJGF5QCuMLQ6hrk

The link to the guideline by NHS Dorset can be found here:

·      https://nhsdorset.nhs.uk/Downloads/aboutus/medicines-management/Other%20Guidelines/Management%20of%20hypomagnesaemia%20in%20primary%20care%20Jan%2023%20-%20Copy.pdf?boxtype=pdf&g=false&s=true&s2=false&r=wide

The link to the guideline by NHS Kent and Medway can be found here:

·      https://www.dgsdvhformulary.nhs.uk/media/1168/hypomagnesaemia-in-adults-primary-care-guide.pdf

The link to the guideline by NHS Lanarkshire can be found here:

·      https://rightdecisions.scot.nhs.uk/media/1539/hypomagnesaemia-in-primary-or-secondary-care.pdf

The link to the guideline by Gloucestershire Hospitals NHS Trust can be found here:

·      https://www.gloshospitals.nhs.uk/media/documents/Hypomagnesaemia_jcPg0oV.pdf

The link to the guideline by Royal Cornwall Hospitals NHS Trust can be found here:

·      https://doclibrary-rcht.cornwall.nhs.uk/DocumentsLibrary/RoyalCornwallHospitalsTrust/Clinical/Pharmacy/TreatmentOfHypomagnesaemiaInAdultsClinicalGuideline.pdf

The link to the guideline by Worcestershire Acute Hospitals NHS Trust can be found here:

·      https://apps.worcsacute.nhs.uk/KeyDocumentPortal/Home/DownloadFile/1559

The link to the MHRA advice on hypomagnesaemia associated to long term PPI use can be found here:

·      https://www.gov.uk/drug-safety-update/proton-pump-inhibitors-in-long-term-use-reports-of-hypomagnesaemia

Disclaimer:

The Video Content on this channel is for educational purposes and not intended to be a substitute for professional medical advice, diagnosis, or treatment. Always seek the advice of your physician or other qualified health provider with any questions you may have regarding a medical condition. Never disregard professional medical advice or delay in seeking it because of something you have read or seen on this YouTube channel. The statements made throughout this video are not to be used or relied on to diagnose, treat, cure or prevent health conditions.

In addition, transmission of this Content is not intended to create, and receipt by you does not constitute, a physician-patient relationship with Dr Fernando Florido, his employees, agents, independent contractors, or anyone acting on behalf of Dr Fernando Florido.

Transcript

If you are listening to this podcast on YouTube, for a better experience, switch to the video version. The link is in the top right corner of the video and in the episode description.

Hello and welcome, I am Fernando, a GP in the UK. Today, we will go through the assessment and management of hypomagnesemia, focusing on what is relevant in Primary Care only. For this advice I have looked at the published guidance by a number of NHS organisations in the UK including Dorset, Lanarkshire, Gloucestershire, Cornwall and Kent and Medway. The links to them are in the episode description.

Right, let’s jump into it.

Hypomagnesaemia is defined as a serum magnesium concentration below 0.7 mmol/L. The normal reference range for serum magnesium is between 0.7 and 1.0 or 1.05 mmol/L, depending on the guideline used.

Magnesium is the second most abundant intracellular electrolyte after potassium, and is an essential cofactor in numerous enzyme systems. It also regulates the transport of calcium and potassium across cell membranes, contributing to neuromuscular conduction, muscle contraction, and cardiac rhythm.

The majority of total body magnesium is stored in bone and soft tissue and only around 1% is in extracellular fluid. Therefore, serum levels may not accurately reflect total body stores. It is possible to see a normal serum level when there is a total body magnesium deficit like in a chronic magnesium deficiency secondary to inadequate dietary magnesium. The reverse, that is, a low serum level and normal total body magnesium, is also possible and is usually seen with drugs which increase excretion of magnesium. Additionally, approximately 25% of plasma magnesium is bound to albumin, so high or low albumin states can also affect the magnesium levels.

Changes in magnesium levels usually occur gradually over months or years and symptoms are often absent, particularly when serum levels are only mildly reduced. They become more common when concentrations fall below 0.5 mmol/L, but there are times when they may also occur in the 0.5–0.7 mmol/L range.

The most common symptoms are:

Muscular and mobility symptoms, including muscle weakness, tremors, ataxia, spasms, fasciculations.

Neurological symptoms, including dizziness, paraesthesia, hallucinations, delirium, seizures, depression, confusion, and coma.

Cardiovascular symptoms, including ECG abnormalities, arrhythmias, and increased sensitivity to digoxin.

Metabolic effects including altered glucose homeostasis, and associations with hypocalcaemia and hypokalaemia.

And finally, other symptoms such as anorexia, nausea, vomiting, and fatigue,

But let’s go back for a moment and ask, why is low magnesium associated with hypocalcaemia and hypokalaemia?

Low magnesium can lead to hypocalcaemia because magnesium is required for the release of PTH. When magnesium is very low, PTH secretion decreases, which leads to reduced calcium reabsorption in the kidneys and reduced calcium release from bone, resulting in low calcium levels.

And what about hypokalaemia? Here the mechanism is connected cellular pumps that regulate intra and extracellular potassium homeostasis which leads to increased renal potassium loss, causing potassium levels to decrease.

Both the hypocalcaemia and hypokalaemia may be refractory to treatment until magnesium is corrected

Let’s now look at the causes and risk factors of hypomagnesemia.

The first cause is Reduced Intake, reduced Absorption or increased gut losses like in:

• Malabsorption (including coeliac disease, Crohn’s disease, and short bowel syndrome)
• Malnutrition and anorexia nervosa
• Chronic diarrhoea
• And excess alcohol intake

Increased Renal Loss like in:

• Renal tubular disorders
• Diabetes and diabetic ketoacidosis
• Hyperaldosteronism
• Hyperthyroidism
• And vitamin D deficiency

Drug-Induced like for example with the use of:

• Proton pump inhibitors (PPIs)
• Both loop and thiazide Diuretics
• Theophylline
• Some chemotherapy agents
• And Digoxin, also bearing in mind that low magnesium may increase digoxin toxicity

And finally Miscellaneous causes such as

·      Acute pancreatitis

·      and excessive lactation

We should prioritise the monitoring of magnesium in patients taking multiple risk drugs or with two or more risk factors.

But let’s pause for a moment. Did we just say that vit D deficiency also causes hypomagnesaemia? And why is that?

Well, in fact, the relationship between magnesium and vitamin D is bidirectional, that is, each influences the metabolism and availability of the other. For example, vitamin D deficiency can cause or worsen hypomagnesaemia by reducing magnesium intestinal absorption and indirectly increasing its renal loss. Conversely, magnesium is a cofactor in the enzymatic steps that convert vitamin D to its active form and, as a result, magnesium deficiency can impair vitamin D activation and function.

Therefore, both deficiencies often coexist, especially in patients with malabsorption, chronic disease, or poor nutrition, and they may exacerbate each other.

Also, of all the drugs mentioned before, PPIs are probably the most commonly and widely prescribed. Because of reported cases of severe hypomagnesaemia associated with prolonged PPI use, normally after 1 year but sometimes as early as 3 months, the MHRA has published a drug safety alert advising healthcare professionals to:

• Consider baseline magnesium measurement before starting PPIs and to
• Monitor magnesium periodically during prolonged treatment, particularly in patients on diuretics or digoxin

We also need to reiterate that for patients on PPIs, symptoms may develop insidiously and be overlooked. PPI related hypomagnesaemia generally resolves upon magnesium replacement and discontinuation of the PPI.

PPIs can also be obtained over-the-counter but patients are advised not to take them for more than 4 weeks without consulting a doctor.

Hypomagnesemia can be graded as:

• Mild: when the levels are below 0.7 but above 0.50 (i.e. 0.51–0.69 mmol/L)
• Moderate: when the levels are 0.50 or below but above 0.40 (i.e. 0.41–0.50 mmol/L)
• And Severe: when the levels are 0.40 mmol/L or below. Here, urgent referral is advised, especially if symptomatic or with concurrent low potassium or calcium.

Let’s now look at the General Principles of management. We will:

• Treat underlying causes
• Discontinue offending drugs where possible (seeking advice if not feasible)
• Consider switching PPIs to H2 antagonists (e.g. famotidine, or nizatidine)
• And we will bear in mind that oral replacement is preferred for asymptomatic mild or moderate deficiencies whereas IV magnesium is required for severe deficiency, symptomatic moderate deficiency or if oral supplements are not tolerated

For Oral Replacement, we will look at the BNF, being aware that magnesium preparations may not be interchangeable due to differences in bioavailability, therefore we should exercise caution when switching between them.

Usually the first-line treatment is with:

• Magnesium aspartate (or Magnaspartate®) which comes in sachets and is preferred for all ages above 2 years

Second-line options include:

• Magnesium glycerophosphate tablets and
• Magnesium citrate

Another oral option includes:

• Magnesium glycerophosphate in liquid form, which is unlicensed but is sometimes used when there are tolerability issues.

Additionally,

• Magnesium sulphate can be administered in secondary care by intravenous infusion, or by intramuscular injection

And let’s remember that IV Replacement is required:

• In severe hypomagnesemia, when Serum magnesium is 0.4 mmol/L o r below
• In symptomatic Moderate hypomagnesaemia, that is, when magnesium is between 0.4 and 0.5 and there are symptoms and also
• Any low level in a patient on digoxin with symptoms

Possible Adverse Effects of oral magnesium include diarrhoea, so we should recommend having it with meals to reduce gastrointestinal irritation.

We should also bear in mind that oral magnesium reduces the absorption of:

• Bisphosphonates
• Tetracyclines and
• Quinolone antibiotics

In terms of monitoring and Follow-Up we should obviously:

• Monitor serum magnesium during and after replacement
• Then continue rechecking at regular intervals in patients with ongoing risk factors
• But also monitor for symptoms of hypermagnesaemia, particularly in renal impairment. Possible symptoms of hypermagnesaemia or high magnesium levels include Respiratory depression, loss of reflexes, confusion, vomiting, cardiac arrhythmias, and coma. Cardiac arrest may occur at levels above 6 mmol/L.

And let’s finish with a quick overview of recommended Patient Education. Patients who are at risk of hypomagnesemia, particularly those on long term PPIs, should be advised to

• Report symptoms such as tremor, vomiting, tiredness, muscle cramps, loss of appetite and fatigue
• They should also increase magnesium-rich foods including green vegetables, wholemeal grains, nuts, pulses, and seafood
• We should also advise them that “Hard” water also contains magnesium salts
• And advise OTC magnesium supplements if there are no clinical concerns such as, for example, severe renal impairment, heart block, bradycardia, or myasthenia gravis.

So that is it, a review of the guidance on the assessment and management of hypomagnesaemia.

We have come to the end of this episode. Remember that this is not medical advice but only my summary and my interpretation of the guidelines. You must always use your clinical judgement.

Thank you for listening and goodbye.