Hypermagnesemia

5.4K views
hypermagnesemia

Hypermagnesemia

Hypermagnesemia is a serum magnesium concentration > 2.6 mg/dL (> 1.05 mmol/L) 1. Hypermagnesemia is an uncommon laboratory finding and symptomatic hypermagnesemia is even less common 2. Hypermagnesemia has a low incidence of occurrence, because the kidney is able to eliminate excess magnesium by rapidly reducing its tubular reabsorption to almost negligible amounts. The major cause of hypermagnesemia (magnesium excess) is renal failure with decreased ability of the kidneys to excrete magnesium. Hypermagnesemia may also be seen with the ingestion of antacids that contain magnesium. Symptomatic hypermagnesemia usually occurs in elderly individuals and in patients with bowel disorders or renal insufficiency in the setting of excessive magnesium ingestion 3. In people with normal kidney function, the kidneys have a very large capacity for magnesium excretion. However, in dialysis patients, the dialysis plays a main role in magnesium removal, such that serum and dialysate magnesium concentrations are related, with both being normal or slightly elevated, depending on the dialysis solution used for these patients 4. Hypermagnesemia symptoms include nausea, muscle weakness, loss of appetite, hypotension, respiratory depression, irregular heart rate and cardiac arrest. Hypermagnesemia diagnosis is by measurement of serum magnesium concentration. Hypermagnesemia treatment includes IV administration of calcium gluconate and possibly furosemide; hemodialysis can be helpful in severe cases.

Magnesium, an abundant mineral in the body, is naturally present in many foods, added to other food products, available as a dietary supplement, and present in some medicines (such as antacids and laxatives). Magnesium is a cofactor in more than 300 enzyme systems that regulate diverse biochemical reactions in the body, including protein synthesis, muscle and nerve function, blood glucose control, and blood pressure regulation 5. Magnesium is required for energy production, oxidative phosphorylation, and glycolysis. It contributes to the structural development of bone and is required for the synthesis of DNA, RNA, and the antioxidant glutathione. Magnesium also plays a role in the active transport of calcium and potassium ions across cell membranes, a process that is important to nerve impulse conduction, muscle contraction, and normal heart rhythm 5.

An adult body contains approximately 25 g magnesium, with 50% to 60% present in the bones and most of the rest in soft tissues 6. Less than 1% of total magnesium is in blood serum, and these levels are kept under tight control. Normal serum magnesium concentrations range between 0.75 and 0.95 millimoles (mmol)/L 7. Magnesium homeostasis is largely controlled by the kidney, which typically excretes about 120 mg magnesium into the urine each day 8. Urinary excretion is reduced when magnesium status is low 9.

Magnesium homeostasis involves the kidney (primarily through the proximal tubule, the thick ascending loop of Henle, and the distal tubule), small bowel (primarily through the jejunum and ileum), and bone. In healthy adults, plasma magnesium ranges from 1.7-2.3 mg/dL. Approximately 30% of total plasma magnesium is protein-bound and approximately 70% is filterable through artificial membranes (15% complexed, 55% free magnesium (Mg2+) ions). With a glomerular filtration rate (GFR) of approximately 150 L per day and an ultrafiltrable magnesium concentration of 14 mg/L, the filtered magnesium load is approximately 2,100 mg per day.

Normally, only 3% of filtered magnesium appears in urine; thus, 97% is reabsorbed by the renal tubules. In contrast to sodium and calcium, only approximately 25-30% of filtered magnesium is reabsorbed in the proximal tubule. Approximately 60-65% of filtered magnesium is reabsorbed in the thick ascending loop of Henle and 5% is reabsorbed in the distal nephron 10. Relatively little is known about cellular magnesium transport mechanisms 11.

Normally, only about 1% of total body magnesium is present inside cells or in bone and this makes it difficult to get an accurate measurement of total magnesium content from blood tests alone 5. The most commonly used and readily available method for assessing magnesium status is measurement of serum magnesium concentration, even though serum levels have little correlation with total body magnesium levels or concentrations in specific tissues 12. Other methods for assessing magnesium status include measuring magnesium concentrations in erythrocytes, saliva, and urine; measuring ionized magnesium concentrations in blood, plasma, or serum; and conducting a magnesium-loading (or “tolerance”) test. No single method is considered satisfactory 13. Some experts [4] but not others 5 consider the tolerance test (in which urinary magnesium is measured after parenteral infusion of a dose of magnesium) to be the best method to assess magnesium status in adults. To comprehensively evaluate magnesium status, both laboratory tests and a clinical assessment might be required 12.

What causes hypermagnesemia?

The most common cause of hypermagnesemia is renal failure. Other causes include the following 14:

  • Excessive intake
  • Lithium therapy
  • Hypothyroidism
  • Addison disease
  • Familial hypocalciuric hypercalcemia
  • Milk alkali syndrome
  • Depression

Renal failure

Patients with end-stage renal disease often have mild hypermagnesemia, and the ingestion of magnesium-containing medications (eg, antacids, cathartics) can exacerbate the condition 15. In patients undergoing regular dialysis, the serum magnesium level directly relates to the dialysate magnesium concentration 16.

In patients with acute renal failure, hypermagnesemia usually presents during the oliguric phase; the serum magnesium level returns to normal during the polyuric phase. If a patient receives exogenous magnesium during the oliguric phase, severe hypermagnesemia can result, especially if the patient is acidotic.

Other causes

People often take magnesium-containing medications (eg, antacids 17, laxatives 18, enemas). Hypermagnesemia can develop after treatment of drug overdoses with magnesium-containing cathartics 19 and it also occurs in patients taking magnesium-containing medications for therapeutic purposes 20; however, most of these patients have normal renal function 21.

With certain gastrointestinal disorders (eg, gastritis, colitis, gastric dilation), increased absorption of magnesium may lead to hypermagnesemia even if the patient does not ingest a large amount of magnesium 22. In any case, monitoring serum magnesium levels in patients taking magnesium-containing medications is prudent. Suicide attempts using magnesium-containing salt can lead to life-threatening hypermagnesemia, as well 23.

Excessive tissue breakdown (sepsis, shock, large burns), especially with concurrent renal failure, can deliver a large amount of magnesium from the intracellular space, along with a massive elevation of phosphorus and potassium 24.

In the treatment of eclampsia, hypermagnesemia is induced deliberately and sometimes can be symptomatic 25. Occasionally, hypermagnesemia also can occur in the newborn infant 26. Maternal magnesium therapy can increase the need for feeding and respiratory support 27 and may cause neurobehavioral disorders in the newborn 28.

Magnesium-containing phosphorus binders are rarely used in end-stage renal disease patients 29 and can lead to elevated magnesium levels.

Lithium therapy causes hypermagnesemia by decreasing urinary excretion, although the mechanism for this is not completely clear.

Familial hypocalciuric hypercalcemia may cause modest elevations in serum magnesium 30. This autosomal dominant disorder is characterized by very low excretion of calcium and magnesium and by a normal parathyroid hormone level. Abnormalities of calcium and magnesium handling are due to mutations in the calcium-sensing receptor 31, resulting in increased magnesium reabsorption in the loop of Henle. More recently, mutations of the codon Arg15 (p.R15) in the adaptor-related protein complex 2, σ-2 subunit that interacts with the calcium-sensing receptor have been described 32.

Hypothyroidism, adrenal insufficiency, milk-alkali syndrome 24 and theophylline intoxication occasionally produce mild elevations of serum magnesium.

There has been some interest in the use of magnesium in the treatment and prevention of cardiac arrhythmias and in the treatment of subarachnoid hemorrhage 33. However, significant hypermagnesemia has not been reported in these settings.

The role of mild elevation of serum magnesium levels in select patient populations is still being defined. In a study examining the prevalence of serum magnesium (Mg) alterations and outcomes in 65,974 hospitalized adult patients, Mg levels of 2.1 mg/dL or higher were found in 20,777 patients (31.5%). An elevated Mg level of 2.3 mg/dL or higher was a predictor of adverse outcomes and associated with worse hospital mortality 34.

In a different study by the same authors, both hypomagnesemia (<1.5 mg/dL) and hypermagnesemia (>2.3 mg/dl) on hospital admission were associated with an increased risk of developing in-hospital acute respiratory failure 35.

In patients admitted to intensive care units, initial magnesium levels ≥2.4 mg/dL (reference: 2.0 to <2.2 mg/dL) was independently associated with increased in mortality 36. In a large study of 5339 critically ill patients from Switzerland, hypermagnesemia was a strong independent risk factor for 28-day mortality 37.

Similarly, in patients with chronic heart failure, a meta-analysis of 7 prospective studies with a total of 5172 subjects demonstrated that those with baseline hypermagnesemia had a significantly higher risk of cardiovascular mortality or all-cause mortality 38. On the other hand, in end-stage renal disease patients on dialysis—a population characterized by a particularly high mortality rate—a mild elevation of serum magnesium appeared protective against cardiovascular mortality, albeit without impacting all-cause mortality 39.

Hypermagnesemia signs and symptoms

Hypermagnesemia signs and symptoms depends on serum magnesium concentrations. Symptomatic hypermagnesemia is fairly uncommon. It occurs most commonly in patients with renal failure after ingestion of magnesium-containing drugs, such as antacids or purgatives.

Symptoms of hypermagnesemia usually are not apparent unless the serum magnesium level is greater than 2 mmol/L 2. Concomitant hypocalcemia, hyperkalemia, or uremia exaggerate the symptoms of hypermagnesemia at any given level.

Signs and symptoms of mild hypermagnesemia are usually subtle and nonspecific and may include flushing, warmth, nausea, headache, and lightheadedness 40. However, magnesium concentrations of 6-12 mg/dL (5-10 mEq/L) result in characteristic electrocardiogram (ECG) changes, including prolongation of the PR interval, increased duration of QRS complex, prolonged QT interval, delayed intraventricular condiction, and increased height of the T wave, changes similar to those of hyperkalemia. Magnesium concentrations of 9-12 mg/dL may induce somnolence, loss of deep tendon reflex, and hypotension, and concentrations >12 mg/dL (10 mEq/L) may result in sinoatrial and atrioventricular block, ventricular arrhythmias, muscle paralysis, hypoventilation, and stupor. Serum magnesium concentrations exceeding 15.6 mg/dL (13 mEq/L) may result in cardiac asystole, coma and respiratory arrest 41.

Nonspecific hypermagnesemia symptoms include the following:

  • Shortness of breath
  • Nausea
  • Vomiting
  • Cutaneous flushing

Neuromuscular symptoms

These are the most common presenting problems. Hypermagnesemia causes blockage of neuromuscular transmission by preventing presynaptic acetylcholine release and by competitively inhibiting calcium influx into the presynaptic nerve channels via the voltage-dependent calcium channel 42.

One of the earliest symptoms of hypermagnesemia is deep-tendon reflex attenuation. Facial paresthesias also may occur at moderate serum levels.

Muscle weakness is a more severe manifestation, occurring at levels greater than 5 mmol/L. This manifestation can result in flaccid muscle paralysis and depressed respiration and can eventually progress to apnea.

Conduction system symptoms

Hypermagnesemia depresses the conduction system of the heart and sympathetic ganglia 42. A moderate increase in serum magnesium can lead to a mild decrease in blood pressure, and a greater concentration may cause severe symptomatic hypotension. Magnesium is also cardiotoxic and, in high concentrations, can cause bradycardia. Occasionally, complete heart block and cardiac arrest may occur at levels greater than 7 mmol/L.

Hypocalcemia

Apparently, hypocalcemia can result from a decrease in the secretion of parathyroid hormone (PTH) or from end-organ resistance to parathyroid hormone (PTH) 43. In patients with end-stage renal disease, high magnesium levels are associated with relative suppression of parathyroid hormone (PTH) 43, which may, in turn, contribute to hypocalcemia in this population.

Paralytic ileus develops from smooth-muscle paralysis 44 and mothers being treated with magnesium for preterm labor suppression are at risk 45.

Hypermagnesemia may interfere with blood clotting through interference with platelet adhesiveness, thrombin generation time, and clotting time.

Hypermagnesemia diagnosis

Hypermagnesemia usually results from a combination of excess magnesium intake and a coexisting impairment of renal function. Diagnosis is usually straightforward and involves measuring serum magnesium levels, as many cases are unsuspected 46. If a magnesium level is not immediately available, a clue to the existence of hypermagnesemia would be the disease context (preeclampsia, renal failure), the presence of magnesium-containing preparations, or a decreased anion gap.

Hypermagnesemia is defined as a serum magnesium concentration > 2.6 mg/dL (> 1.05 mmol/L).

At serum magnesium concentrations of 6 to 12 mg/dL (2.5 to 5 mmol/L), the electrocardiogram (ECG) shows prolongation of the PR interval, widening of the QRS complex, and increased T-wave amplitude. Deep tendon reflexes disappear as the serum magnesium concentration approaches 12 mg/dL (5.0 mmol/L); hypotension, respiratory depression, and narcosis develop with increasing hypermagnesemia. Cardiac arrest may occur when blood magnesium concentration is > 15 mg/dL (6.0 to 7.5 mmol/L).

Hypermagnesemia treatment

Treatment of severe magnesium toxicity consists of circulatory and respiratory support and administration of 10% calcium gluconate 10 to 20 mL IV. Calcium gluconate may reverse many of the magnesium-induced changes, including respiratory depression.

Administration of IV furosemide can increase magnesium excretion when renal function is adequate; volume status should be maintained.

Hemodialysis may be valuable in severe hypermagnesemia, because a relatively large fraction (about 70%) of blood magnesium is not protein bound and thus is removable with hemodialysis. When hemodynamic compromise occurs and hemodialysis is impractical, peritoneal dialysis is an option.

  1. Hypermagnesemia. https://www.merckmanuals.com/professional/endocrine-and-metabolic-disorders/electrolyte-disorders/hypermagnesemia[↩]
  2. Hypermagnesemia. https://emedicine.medscape.com/article/246489-overview[↩][↩]
  3. Onishi S, Yoshino S. Cathartic-induced fatal hypermagnesemia in the elderly. Intern Med. 2006;45:207–210[↩]
  4. Musso CG. Magnesium metabolism in health and disease. Int Urol Nephrol. 2009;41:357–362.[↩]
  5. Rude RK. Magnesium. In: Ross AC, Caballero B, Cousins RJ, Tucker KL, Ziegler TR, eds. Modern Nutrition in Health and Disease. 11th ed. Baltimore, Mass: Lippincott Williams & Wilkins; 2012:159-75.[↩][↩][↩][↩]
  6. Volpe SL. Magnesium. In: Erdman JW, Macdonald IA, Zeisel SH, eds. Present Knowledge in Nutrition. 10th ed. Ames, Iowa; John Wiley & Sons, 2012:459-74.[↩]
  7. Elin RJ. Assessment of magnesium status for diagnosis and therapy. Magnes Res 2010;23:1-5.[↩]
  8. Rude RK. Magnesium. In: Coates PM, Betz JM, Blackman MR, Cragg GM, Levine M, Moss J, White JD, eds. Encyclopedia of Dietary Supplements. 2nd ed. New York, NY: Informa Healthcare; 2010:527-37.[↩]
  9. Institute of Medicine (IOM). Food and Nutrition Board. Dietary Reference Intakes: Calcium, Phosphorus, Magnesium, Vitamin D and Fluoride. Washington, DC: National Academy Press, 1997.[↩]
  10. Quamme GA. Control of magnesium transport in the thick ascending limb. Am J Physiol. 1989 Feb. 256(2 Pt 2):F197-210[↩]
  11. Musso CG. Magnesium metabolism in health and disease. Int Urol Nephrol. 2009 Mar 10.[↩]
  12. Gibson, RS. Principles of Nutritional Assessment, 2nd ed. New York, NY: Oxford University Press, 2005.[↩][↩]
  13. Witkowski M, Hubert J, Mazur A. Methods of assessment of magnesium status in humans: a systematic review. Magnesium Res 2011;24:163-80.[↩]
  14. Drueke TB, Lacour B. Disorders of calcium, phosphate and magnesium metabolism. Feehally J, Floege J, Johnson RJ, eds. Comprehensive Clinical Nephrology. 3rd ed. Philadelphia, Pa: Mosby; 2007. 137-8.[↩]
  15. Alaini A, Roldan CA, Servilla K, Colombo ES. Near death by milk of magnesia. BMJ Case Rep. 2017 Mar 21. 2017[↩]
  16. Navarro-Gonzalez JF, Mora-Fernandez C, Garcia-Perez J. Clinical implications of disordered magnesium homeostasis in chronic renal failure and dialysis. Semin Dial. 2009 Jan-Feb. 22(1):37-44[↩]
  17. Torikoshi-Hatano A, Namera A, Shiraishi H, Maeno Y, Kato H, Nagao M. A fatal case of hypermagnesemia caused by ingesting magnesium chloride as a folk remedy. J Forensic Sci. 2013 Nov. 58(6):1673-5.[↩]
  18. Karahan MA, Kucuk A, Buyukfirat E, Yalcin F. Acute Respiratory and Renal Failure due to Hypermagnesemia, Induced by Counter Laxatives in an Elderly Man. J Clin Diagn Res. 2015 Dec. 9 (12):UL01.[↩]
  19. Woodard JA, Shannon M, Lacouture PG, et al. Serum magnesium concentrations after repetitive magnesium cathartic administration. Am J Emerg Med. 1990 Jul. 8(4):297-300.[↩]
  20. So M, Ito H, Sobue K, et al. Circulatory collapse caused by unnoticed hypermagnesemia in a hospitalized patient. J Anesth. 2007. 21(2):273-6.[↩]
  21. Rahman A, Vanner SJ, Baranchuk A, Hookey LC. Serial monitoring of the physiological effects of the standard Pico-Salax® regimen for colon cleansing in healthy volunteers. Can J Gastroenterol. 2012 Jul. 26(7):424-8.[↩]
  22. Sugiyama M, Kusumoto E, Ota M, Kimura Y, Tsutsumi N, Oki E, et al. Induction of potentially lethal hypermagnesemia, ischemic colitis, and toxic megacolon by a preoperative mechanical bowel preparation: report of a case. Surg Case Rep. 2016 Dec. 2 (1):18.[↩]
  23. Jung HM, Paik JH, Kim JH, Han SB. A case report of bittern intoxication. J Emerg Trauma Shock. 2015 Apr-Jun. 8 (2):108-9.[↩]
  24. Bringhurst FR, Demay MB, Krane SM, et al. Bone and mineral metabolism in health and disease/hypermagnesemia. Kasper DL, et al, eds. Harrison’s Principles of Internal Medicine. 16th ed. New York, NY: McGraw-Hill; 2005. 2245.[↩][↩]
  25. Al-Shoha M, Klair JS, Girotra M, Garcia-Saenz-de-Sicilia M. Magnesium Toxicity-Induced Ileus in a Postpartum Patient Treated for Preeclampsia With Magnesium Sulphate. ACG Case Rep J. 2015 Jul. 2 (4):227-9.[↩]
  26. Hyun HS, Choi HS, Kim JK, Ahn SY, Yoo HS, Kim ES, et al. Idiopathic severe hypermagnesemia in an extremely low birth weight infant on the first day of life. Korean J Pediatr. 2011 Jul. 54(7):310-2[↩]
  27. Greenberg MB, Penn AA, Whitaker KR, Kogut EA, El-Sayed YY, Caughey AB, et al. Effect of magnesium sulfate exposure on term neonates. J Perinatol. 2013 Mar. 33(3):188-93.[↩]
  28. Rasch DK, Huber PA, Richardson CJ, et al. Neurobehavioral effects of neonatal hypermagnesemia. J Pediatr. 1982 Feb. 100(2):272-6.[↩]
  29. Wyskida K, Witkowicz J, Chudek J, Wiecek A. Daily magnesium intake and hypermagnesemia in hemodialysis patients with chronic kidney disease. J Ren Nutr. 2012 Jan. 22(1):19-26.[↩]
  30. Law WM Jr, Heath H 3rd. Familial benign hypercalcemia (hypocalciuric hypercalcemia). Clinical and pathogenetic studies in 21 families. Ann Intern Med. 1985 Apr. 102(4):511-9.[↩]
  31. Pearce SH, Trump D, Wooding C, et al. Calcium-sensing receptor mutations in familial benign hypercalcemia and neonatal hyperparathyroidism. J Clin Invest. 1995 Dec. 96(6):2683-92.[↩]
  32. Hendy GN, Canaff L, Newfield RS, Tripto-Shkolnik L, Wong BY, Lee BS, et al. Codon Arg15 mutations of the AP2S1 gene: common occurrence in familial hypocalciuric hypercalcemia cases negative for calcium-sensing receptor (CASR) mutations. J Clin Endocrinol Metab. 2014 Jul. 99 (7):E1311-5.[↩]
  33. Schmid-Elsaesser R, Kunz M, Zausinger S, et al. Intravenous magnesium versus nimodipine in the treatment of patients with aneurysmal subarachnoid hemorrhage: a randomized study. Neurosurgery. 2006 Jun. 58(6):1054-65; discussion 1054-65.[↩]
  34. Cheungpasitporn W, Thongprayoon C, Qian Q. Dysmagnesemia in Hospitalized Patients: Prevalence and Prognostic Importance. Mayo Clin Proc. 2015 Aug. 90 (8):1001-10.[↩]
  35. Thongprayoon C, Cheungpasitporn W, Srivali N, Erickson SB. Admission serum magnesium levels and the risk of acute respiratory failure. Int J Clin Pract. 2015 Nov. 69 (11):1303-8.[↩]
  36. Naksuk N, Hu T, Krittanawong C, Thongprayoon C, Sharma S, Park JY, et al. Association of Serum Magnesium on Mortality in Patients Admitted to the Intensive Cardiac Care Unit. Am J Med. 2017 Feb. 130 (2):229.e5-229.e13[↩]
  37. Haider DG, Lindner G, Ahmad SS, Sauter T, Wolzt M, Leichtle AB, et al. Hypermagnesemia is a strong independent risk factor for mortality in critically ill patients: results from a cross-sectional study. Eur J Intern Med. 2015 Sep. 26 (7):504-7.[↩]
  38. Angkananard T, Anothaisintawee T, Eursiriwan S, Gorelik O, McEvoy M, Attia J, et al. The association of serum magnesium and mortality outcomes in heart failure patients: A systematic review and meta-analysis. Medicine (Baltimore). 2016 Dec. 95 (50):e5406[↩]
  39. Yu L, Li H, Wang SX. Serum Magnesium and Mortality in Maintenance Hemodialysis Patients. Blood Purif. 2017. 43 (1-3):31-36.[↩]
  40. Jhang WK, Lee YJ, Kim YA, Park SJ, Park YS. Severe hypermagnesemia presenting with abnormal electrocardiographic findings similar to those of hyperkalemia in a child undergoing peritoneal dialysis. Korean J Pediatr. 2013;56(7):308–311. doi:10.3345/kjp.2013.56.7.308 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3728451[↩]
  41. Topf JM, Murray PT. Hypomagnesemia and hypermagnesemia. Rev Endocr Metab Disord. 2003;4:195–206.[↩]
  42. Agus ZS, Morad M. Modulation of cardiac ion channels by magnesium. Annu Rev Physiol. 1991. 53:299-307.[↩][↩]
  43. Ohya M, Negi S, Sakaguchi T, Koiwa F, Ando R, Komatsu Y, et al. Significance of serum magnesium as an independent correlative factor on the parathyroid hormone level in uremic patients. J Clin Endocrinol Metab. 2014 Oct. 99 (10):3873-8.[↩][↩]
  44. Clark BA, Brown RS. Unsuspected morbid hypermagnesemia in elderly patients. Am J Nephrol. 1992. 12(5):336-43.[↩]
  45. Cruikshank DP, Pitkin RM, Reynolds WA, et al. Effects of magnesium sulfate treatment on perinatal calcium metabolism. I. Maternal and fetal responses. Am J Obstet Gynecol. 1979 Jun 1. 134(3):243-9.[↩]
  46. Whang R, Ryder KW. Frequency of hypomagnesemia and hypermagnesemia. Requested vs routine. JAMA. 1990 Jun 13. 263(22):3063-4.[↩]

you might also like

Health Jade