Plasma concentrations of magnesium are kept within a very narrow range and are regulated by adjustment in renal excretion, bone uptake, intestinal uptake, and soft tissue stores. Magnesium differs from other ions in two major respects: (1) it is not hormonally regulated, and (2) bone, as the principal storage site for magnesium, does not readily exchange with extracellular magnesium. This inability to mobilize magnesium stores means that in states of negative magnesium balance, initial losses come from the extracellular space, and equilibrium from bone stores does not begin for several weeks (Agraharkar & Fahlen, 2002).

The body contains an average of about 24 total grams of magnesium. Approximately 60% of magnesium is bound to protein, but it is the ionized, unbound magnesium that is ionically active (Topf & Murray, 2003). Despite this fact, ionized calcium levels have not proven to reliably reflect magnesium depletion, and no albumin correction factor has been defined (Topf & Murray, 2005; Dacey, 2001). Magnesium may be reported in mg/dL, mmol, or mEq/L. Plasma concentrations are usually reported in mEq/L, but replacement therapy is administered in units or grams.

The normal plasma magnesium concentration is 1.4 to 1.7 mEq/L (0.7 to 0.9 mmol, or 1.7 to 2.1 mg/dL) (Agraharkar & Fahlen, 2002). Hypomagnesemia is defined as a plasma level less than 1.4 mEq/L (0.7 mmol or 1.6 mg/dL). It is an accepted concept that plasma levels do not always indicate the body’s true status of depletion, yet there are no established methods to define the body’s total magnesium level (Topf & Murray, 2003; Dacey, 2001). Because so little magnesium is located extracellularly, plasma hypomagnesemia often indicates a more severe underlying cellular deficiency. Inability to readily recognize increases in plasma magnesium levels in response to replacement therapy may indicate this intracellular deficiency.

The average American diet contains approximately 360 mg (15 mmol) of magnesium; healthy individuals ingest 0.15 to 0.2 mmol/kg each day to maintain balance (Agraharkar & Fahlen, 2002). Magnesium is absorbed via the small intestine, and the amount absorbed depends on the amount ingested. When dietary ingestion is normal, approximately 30% to 40% is absorbed; when intake is low, approximately 80% is absorbed; if intake is increased (as with oral replacement therapy), only about 25% is absorbed.


Studies of the incidence of hypomagnesemia in the general population are sparse, but its prevalence is estimated to be 1.5% to 15% (Mouw, 2005; Topf & Murray, 2003). Dietary evaluations suggest that magnesium deficiency may be even more prevalent than estimated because of the effects of low dietary intake and the inability of standard testing measures to reflect true intracellular magnesium deficiency (Mouw, 2005; Topf & Murray, 2003). Hypomagnesemia occurs in approximately 12% of hospitalized patients, with the highest incidence in the critically ill (60% to 65%) (Agus, 2006a; Mouw, 2005; Tong & Rude, 2005; Topf & Murray, 2003). A proposed reason for this high incidence in the critically ill is the extent of oxidative stress and inflammation experienced by these patients (Guerrero-Romero & Rodriguez-Moran, 2006).


• Reduced magnesium intake may be the etiology of hypomagnesemia in chronically malnourished individuals. Individuals who have an inadequate intake, an increased fat intake, or a poorly balanced diet that does not include adequate nuts, seeds, fish, or vegetables are more likely to become magnesium deficient. Water in some areas can supplement magnesium.

Gastrointestinal losses: The upper gastrointestinal tract has higher levels of magnesium than the lower intestinal tract (15 mEq/L versus 1 mEq/L), therefore depletion of magnesium is more pronounced with small intestinal disorders such as small bowel obstruction, small bowel resection, or Crohn’s disease (Agus, 2006a). The amount of small bowel resected may directly influence the severity of magnesium deficiency (Topf & Murray, 2003).

• Renal losses of magnesium occur as a result of primary or secondary defects in tubular reabsorption.

• Magnesium deficiency may accompany inhibition of sodium reabsorption, because magnesium passively follows sodium transport (Topf & Murray, 2003).

• Loop and thiazide diuretics inhibit net magnesium reabsorption (Topf & Murray, 2003).

• Volume expansion leads to mild hypomagnesemia as a result of decreased passive transport.

• An excessive alcohol intake has been linked to an approximate 30% incidence of hypomagnesemia as a result of alcohol-induced tubular dysfunction. This tubular abnormally is viewed as temporary and reverses after approximately 4 weeks of abstinence (Elisaf et al., 1995).

• Gitelman’s syndrome is a autosomal recessive familial defect in the sodium-chloride transporter mechanism in the loop of Henle (also called the thiazide-sensitive Na-Cl channel). It is associated with concomitant hypocalciuria. A few case reports of this syndrome have been associated with a history of treatment with cisplatin (Agus, 2006a; Panichpisal et al., 2006).

• Bartter’s syndrome is an X-linked genetic disorder of tubular reabsorption that causes hypocalciuria and hypomagnesemia (Agus, 2006a). The hypomagnesemia is less severe in this familial syndrome than in others (Topf & Murray, 2003).

• Manz syndrome is a rare disorder of absorption in the ascending loop of Henle that causes hypocalcemia and hypomagnesemia with polyuria, nystagmus, and tetany (Akhtar et al., 2006).

• Pancreatitis causes hypomagnesemia accompanied by hypocalcemia through the mechanism of saponification of magnesium and calcium in necrotic fat tissue (Agus, 2006a; Dacey, 2001).

• Hyperparathyroidism-induced hypocalcemia is often linked to concomitant hypomagnesemia. When this etiology is present, the hypocalcemia is refractory to calcium replacement therapy unless magnesium is also repleted (Topf & Murray, 2003).

• Diabetes mellitus, particular with uncontrolled hyperglycemia, causes excessive renal excretion of magnesium, resulting in an incidence of hypomagnesemia of approximately 25% to 40% in patients with diabetes mellitus of any etiology (Tong & Rude, 2005; Topf & Murray, 2003). It has been proposed that hypomagnesemia contributes to impaired glucose utilization and may be instrumental in the pathophysiology of complications of diabetes, such as nephropathy, vascular disease, and retinopathy (Sales & Pedrosa, 2006; Pham et al., 2005).

• The risk of hypomagnesemia with diabetes mellitus is greater in type 2 diabetes (Pham et al., 2005).

• Factors associated with an increased incidence of hypomagnesemia in patients with diabetes mellitus include high plasma triglycerides, waist circumference, and albuminuria (Corica et al., 2006). Glucosuria has also been associated with increased magnesium wasting.

• Uncontrolled glucose levels and the metabolic syndrome are associated with a higher incidence of hypomagnesemia (Sales & Pedrosa, 2006; Corica et al., 2006).

• Postoperative hypomagnesemia may occur as a result of several distinctly different etiologic mechanisms (Agus, 2006a).

• Chelation of circulating free fatty acids (especially after pancreatic and hepatobiliary surgery) causes decreased renal excretion (Topf & Murray, 2003).

• Transfusion of citrate-rich blood products causes hypocalcemia and accompanying hypomagnesemia. This has been noted after traumatic injury and liver transplantation.

• Postoperative parathyroidectomy patients have an induced “hungry bone syndrome” characterized by increased bone uptake of magnesium during bone remineralization, with plasma depletion (Dacey, 2001).

• Postoperative bowel resection causes hypomagnesemia in approximately 20% of patients.

• Variables that influence the incidence of this complication include the preoperative bowel cleansing regimen and the extent of bowel resection (Schwarz & Nevarez, 2005; Topf & Murray, 2003).

• Inflammation of the bowel may exacerbate this problem in the immediate postoperative period.

• Nephrotoxins disrupt the loop of Henle and distal tubular reabsorption of magnesium (Table 30-1). * Some agents, such as the platinol antineoplastics, also alter gastrointestinal absorption of magnesium. With some drugs (e.g., cetuximab), the renal tubular injury resolves, as does the hypomagnesemia (Fakih et al., 2006). However, hypomagnesemia associated with cisplatin therapy has been reported as permanent (Bashir et al., 2006).

Data from Aisa, Y., Mori, T., & Nakazato, T., et al. (2005). Effects of immunosuppressive agents on magnesium metabolism after allogeneic hematopoietic stem cell transplantation. Transplantation, 80:1046-1050; Fakih, M. G., Wilding, G., & Lombardo, J. (2006). Cetuximab-induced hypomagnesemia in patients with colorectal cancer. Clinical Colorectal Cancer, 6(2):152-156; Navaneethan, S. D., Sankarasubbaiyan, S., & Gross, M. D., et al. (2006). Tacrolimus-associated hypomagnesemia in renal transplant recipients. Transplant Proceedings, 38(5):1320-1322; Nawaz, S. H., Zafar, M. N., & Naqvi, S. A., et al. (2005). Impact of cyclosporine immunosuppression on serum magnesium and its fractional excretion in renal transplant recipients. Journal of the Pakistan Medical Association, 55(3):98-100; Pearson, E. C., & Woosley, R. L. (2005). QT prolongation and torsades de pointes among methadone users: Reports to the FDA spontaneous reporting system. Pharmacoepidemiology and Drug Safety, 14(11):747-753; Schrag, D., Chung, K. Y., & Flombaum, C., et al. (2005). Cetuximab therapy and symptomatic hypomagnesemia. Journal of the National Cancer Institute, 97(16):1221-1224; Stohr, W., Paulides, M., & Bielack, S., et al. (2007). Nephrotoxicity of cisplatin and carboplatin in sarcoma patients: A report from the late effects surveillance system. Pediatric Blood Cancer, 48(2):140-147; Thomson Healthcare. (2007). Thomson micromedex healthcare series. Retrieved January 15, 2007, from http://www.thomsonhc.com; Topf, J. M., & Murray, P. T. (2003). Hypomagnesemia and hypermagnesemia. Reviews in Endocrine and Metabolic Disorders, 4:195-206.
Drug Category Examples of Agents






Amphotericin B

Amphotericin lipid complex


Arsenic trioxide


Gallium nitrate

Antiretrovirals, nucleoside reverse transcriptase inhibitors


Antiviral agents Foscarnet





Zoledronic acid
Bowel stimulants




Diuretics, loop type and thiazide type






Immunosuppressive agents


Mycophenolic acid

Miscellaneous azgents



Dextrose solution





Monoclonal antibody antineoplastic agents


Opiates Methadone



Transdermal losses: Excessive sweating or massive burns cause loss of magnesium in as many as 40% of patients (Mouw, 2005; Topf & Murray, 2003; Dacey, 2001).

• Magnesium depletion has been associated with a number of other medical conditions, including acidosis, attention deficit disorder, elevated bilirubin levels, fibromyalgia, hemolysis, hyperglycemia, hypertension, migraine headaches, menopause, pre-eclampsia, stroke, and ulcerative colitis. Symptoms of these disorders may improve with magnesium repletion (Agus, 2006a; Mouw, 2005; Topf & Murray, 2003; Dacey, 2001).


Patients with acute onset of hypomagnesemia from a clearly identifiable cause have an excellent prognosis for complete recovery from this condition. In conditions of chronic loss, correction of the disorder and its symptoms may be a continuous challenge, although death attributable solely to hypomagnesemia is rare. Despite this lack of evidence regarding the importance of magnesium contributory to death, studies of intensive care patients have shown that the mortality rate is two to three times higher among patients with hypomagnesemia (Topf & Murray, 2003; Rubeiz et al., 1993).


1. The primary clinical manifestations of hypomagnesemia are neuromuscular in nature. Increased or hyperactive neuromuscular function is the predominant feature. This is manifested similarly to findings of hypocalcemia and hypokalemia. Common symptoms include:

• Mood disturbances, such as apathy and depression (Agus, 2006c; Perrin et al., 2006).

• Seizures (in more severe deficiency, defined as a plasma magnesium less than 1 mEq/L) (Dharnidharka & Carney, 2005; Dacey, 2001).

• Extrapyramidal symptoms (e.g., nystagmus, tremors).

• Cortical blindness (reversible with magnesium replenishment) (Topf & Murray, 2003).

• Tetany (prolonged, painful muscle contraction).

• Respiratory muscle weakness, which can lead to shallow breathing, decreased respiratory effort, and hypercarbia.

• Paresthesias

• Increased skeletal muscle sensitivity to nerve stimulation, as evidenced by tetany in response to nerve pressure. Although these clinical findings are classic symptoms of hypocalcemia, they may be present with hypomagnesemia even without depleted calcium.
Oct 19, 2016 | Posted by in NURSING | Comments Off on 30. HYPOMAGNESEMIA

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