Hypomagnesaemia

OVERVIEW

• Defined as serum magnesium < 0.75 mmol/L
• Hypomagnesaemia is associated with increased ICU mortality
• common —  affects 10-65% of ICU patients

CAUSES

Decreased intake

• Protein calorie malnutrition
• Enteral nutrition
• Alcoholism
• Total parenteral nutrition (TPN)
• Malabsorption — e.g. Gastric-bypass surgery, Chronic Pancreatitis, Sprue, Steatorrhea, Congenital malabsorption, Inflammatory bowel disease
• Proton pump inhibitors (mechanism unclear, likely decreased GI absorption)

Increased loss

• GI — nasogastric drainage, Diarrhoea, Vomiting
• Increased renal tubular flow — Volume expansion, Osmotic diuresis (hyperglycemia, mannitol), Diuretics (Loop/Thiazide/Osmotic), Antimicrobials (Aminoglycosides, Amphotericin B, Carbapenems, Pentamidine), Chemotherapy (Cisplatin)
• Renal tubular dysfunction — Renal tubular acidosis, Acute tubular necrosis, Urinary tract obstruction, Transplantation
• Hypercalcemia
• Hyperaldosteronism
• Congenital renal magnesium wasting (Gitelman syndrome, Bartter syndrome)

Other causes

• Burns (40% of burns patients have low Mg)
• TEN (Toxic epidermal necrolysis)
• Hungry-bone syndrome
• Acute pancreatitis
• Insulin infusion (intracellular shift due to increase cellular uptake, though insulin also decreases renal excretion of magnesium)

PATHOPHYSIOLOGY

• Effects on membrane potentials
  • Mg deficiency leads to a drop in ICF potassium and a rise in the ICF Na
  • This leads to an elevation in the resting potential, and in turn a rise in the inward Ca current and hence enhanced neurological and cardiac irritability
• magnesium is required for potassium reabsorption by the kidneys
  • likely due to increased activity of renal ATP-dependent ROMK channels (especially in thick ascending loop of Henle and cortical collecting ducts) leading to increased basal potassium excretion)
• hypocalcaemia occurs because magnesium leads to impaired release of PTH and impaired peripheral action of PTH

CLINICAL MANIFESTATIONS

• Symptoms occur usually at levels <0.5mmol/L

CNS

• Neuromuscular irritability
• Trousseau and Chvostek signs (even despite normal ionized calcium)
• Weakness / fatigue (‘lemonade legs’)
• Vertical nystagmus
• Tetany
• Seizures
• Reversible blindness

CVS

• Arrhythmia, especially torsades des pointes (resistant to cardioversion)
• ECG Changes similar to hypokalemia
• Digitalis toxicity

Metabolic

• Resistant hypocalcaemia
• Resistant hypokalaemia
• PTH resistance and impaired PTH release

INVESTIGATIONS

24 hour urine Magnesium

• >24 mg → Renal wasting

Fractional excretion of Mg (FeMg)

• > 4% → Renal wasting

Tissue Magnesium level estimation

• Magnesium load test (800mg infusion over 8 H followed by 24 hour urine Magnesium

Other

• Only ionized magnesium (60% of total plasma Magnesium ) is physiologically active, although it is not measured routinely
• Low serum albumin lowers total plasma Mg but ionized Mg may be normal

MANAGEMENT

• Resuscitation — treat dysrhythmias, seizures and other life threats
• Magnesium replacement
  • Intravenous Magnesium replacement – preferred in malabsorption states and acute symptomatic states
  • Oral Magnesium replacement 120mg TDS
• Correct co-existing electrolyte abnormalities (hypokalemia and hypocalcemia)
• Potassium-sparing diuretics for chronic renal magnesium wasting
• Seek and treat underlying cause

ASSOCIATIONS

• Often associated with normal anion gap metabolic acidosis (NAGMA)
• HYPOcalcaemia
• HYPOkalaemia
• HYPOmagnesemia
• HYPERnatremia

REFERENCES AND LINKS

• Ayuk J, Gittoes NJ. Contemporary view of the clinical relevance of magnesium homeostasis. Ann Clin Biochem. 2014;51(Pt 2):179-188. doi:10.1177/0004563213517628
• Ayuk J, Gittoes NJ. How should hypomagnesaemia be investigated and treated?. Clin Endocrinol (Oxf). 2011;75(6):743-746. doi:10.1111/j.1365-2265.2011.04092.x
• Gandhi NY, Sharif WK, Chadha S, Shakher J. A patient on long-term proton pump inhibitors develops sudden seizures and encephalopathy: an unusual presentation of hypomagnesaemia. Case Rep Gastrointest Med. 2012;2012:632721. doi:10.1155/2012/632721
• Herroeder S, Schönherr ME, De Hert SG, Hollmann MW, Warner DS; Magnesium—Essentials for Anesthesiologists. Anesthesiology 2011; 114:971–993 doi: https://doi.org/10.1097/ALN.0b013e318210483d
• Hypomagnesaemia. Drug Ther Bull. 2013;51(3):33-36. doi:10.1136/dtb.2013.1.0169

CCC Differential Diagnosis Series
NEURO	Anosmia, Ataxia, Blepharospasm, Bulbar and Pseudobulbar palsy, Central Pontine Myelinosis, Cerebellar Disease, Chorea, Cranial nerve lesions, Dementia, Dystonia, Exophthalmos, Eye trauma, Facial twitches, Fixed dilated pupil, Horner syndrome, Loss of vision, Meningism, Movement disorders, Optic disc abnormality, Parkinsonism, Peripheral neuropathy, Radiculopathy, Red eye, Retinal Haemorrhage, Seizures, Sudden severe headache, Tremor, Tunnel vision
RESP	Bronchial breath sounds, Bronchiectasis, High airway pressures, Massive haemoptysis, Sore throat, Tracheal displacement
CVS	Atrial Fibrillation, Bradycardia, Cardiac Failure, Chest Pain, Murmurs, Post-resuscitation syndrome, Pulseless Electrical Activity (PEA), Pulsus Paradoxus, Shock, Supraventricular tachycardia (SVT), Tachycardia, VT and VF, SVC Obstruction
GIT	Abdominal distension, Abdominal mass, Abdominal pain, Asterixis, Dysphagia, Hepatomegaly, Hepatosplenomegaly, Large bowel obstruction, Liver palpation abnormalities, Lower GI haemorrhage, Malabsorption, Medical causes of abdominal pain, Rectal mass, Small bowel obstruction, Upper GI Haemorrhage
GUT	Genital ulcers, Groin lump, Scrotal mass, Urine colour, Urine Odour, Urine transparency,
MSK	Arthritis, Shoulder pain, Wasting of the small muscles of the hand
DERM	Palmar erythema, Serious skin signs in sick patients, Thickened Tethered Skin, Leg ulcers, Skin Tumour, Acanthosis Nigricans
ENDO	Diabetes Insipidus, Diffuse Goitre, Gynaecomastia, Hirsutism, Hypoglycaemia, SIADH, Weight Loss
HAEM	Splenomegaly
PAEDS	Floppy infant
MISC	Anaphylaxis, Autoimmune associated diseases, Clubbing, Parotid Swelling, Splinter haemorrhages, Toxic agents and abnormal vitals, Toxicological causes of cardiac arrest
IMAGING	CHEST: Atelectasis, Hilar adenopathy, Hilar enlargement on CXR, Honeycomb lung, Increased interstitial markings, Mediastinal widening on mobile CXR, Pulmonary fibrosis, Pseudoinfiltrates on CXR, Pulmonary opacities on CXR, ABDO: Gas on abdominal X-ray, Kidney mass, BRAIN: Intracranial calcification, Intracranial structures with contrast, Ventriculomegaly, OTHER: Pseudofracture on X-Ray,
LABS	LOW: Anaemia, Hypocalcaemia, hypochloraemia, Hypomagnesaemia,  HIGH: Bilirubin and Jaundice, Hyperammonaemia, Hypercalcaemia, Hyperchloraemia, Hyperkalaemia, Hypermagnesaemia,  ACID BASE: Acid base disorders, Resp. acidosis, Resp. alkalosis, Creatinine, CRP, Dipstick Urinalysis, Laboratory Urinalysis, Liver function tests (LFTs), Pleural fluid analysis, Urea, Urea Creatinine Ratio, Uric acid, Urinalysis, Urine Electrolytes

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