Chapter 8. Disorders of Magnesium Balance: Hypomagnesemia & Hypermagnesemia

General Considerations

Magnesium is the second most abundant intracellular cation and the fourth most common cation in the human body. It plays an essential role in a variety of cellular processes including enzyme activities involving adenosine triphosphate (ATP), energy metabolism, nucleic acid and protein synthesis, regulation of ion channels, and stabilization of membrane structures. The importance of magnesium in the body is reflected in the diverse clinical effects that accompany disorders of magnesium homeostasis. The average size adult contains approximately 24 g (1 mol, 2000 mEq) of magnesium. It is predominantly stored in bone (55–60%) and the intracellular compartments of muscle (20%) and soft tissues (20%) and it exchanges very slowly with extracellular magnesium. Therefore, skeletal and intracellular magnesium is an ineffective buffer in the setting of acute extracellular magnesium loss.

Approximately 1% of total body magnesium is in the extracellular fluid (ECF) and is composed of three fractions: 60–65% is free, ionized, and physiologically active; 30% is protein bound; and the balance is complexed to citrate, phosphate, and other anions. In clinical practice, magnesium status is assessed by measurement of total serum magnesium. Serum magnesium concentrations normally average 1.7–2.3 mg/dL (1.4–2.1 mEq/L). Given the intracellular nature of this cation, serum magnesium concentrations poorly reflect total body status.

Daily magnesium intake in the typical American diet averages 300–360 mg/day. Food sources of magnesium include green vegetables, nuts, and whole grains, as well as some meats and seafood. Of dietary magnesium 30–40% is absorbed in the gut, primarily by the small intestine, with smaller amounts being absorbed in the colon. There is some magnesium in intestinal secretions (approximately 20–40 mg), but under normal circumstances their contribution to overall magnesium elimination is minimal. However, these losses can become quite substantial in diarrheal states or with biliary fistulas.

The kidney is the main organ responsible for magnesium homeostasis. Approximately 70–80% (2.4 g) of the total serum magnesium is filtered by the kidneys. Under normal circumstances 95–97% is reabsorbed by the tubules. The plasma magnesium concentration is the most important determinant of renal magnesium excretion. Less than 5% (120 mg) is normally excreted in urine. However, hypomagnesemia results in conservation of magnesium by normal kidneys leading to a fractional excretion of less than 0.5% (12 mg) per day. Conversely, the kidneys increase excretion of magnesium to approximate the filtered load during periods of increased intake or excess magnesium administration.

In contrast to many of the other electrolytes (ie, Na+, K+, and Ca2+), control of magnesium reabsorption does not appear to be tightly regulated by a specific hormone. Parathyroid hormone, calcitonin, vitamin D, glucagon, antidiuretic hormone, aldosterone, sex steroids, and β-adrenergic agonists can affect magnesium handling in experimental studies, but it is not known if these effects have an important role in humans.

While the proximal tubule is the major site of reabsorption of other ions, only a small percentage (15–25%) of the filterable magnesium is reabsorbed in this segment. Here, magnesium transport is passive, driven by bulk flow, and depends on sodium reabsorption. Factors that affect sodium reabsorption (ie, volume expansion) can also affect magnesium reabsorption. The majority of magnesium reabsorption (60–70%) occurs in the cortical thick ascending limb (TAL) of the loop of Henle. Here again, magnesium reabsorption is a passive, paracellular process and depends on sodium reabsorption. The driving force for the reabsorption of magnesium (and calcium) is the lumen-positive electrical potential generated by sodium chloride reabsorption via the Na+/K+/2Cl− cotransporter in concert with the coordinated activity of the basolateral Na+ − K+-ATPase, a chloride channel, and an apical membrane potassium channel. Disturbances of this coordinated activity at any site (such as with loop diuretics or inherited defects/Bartter's syndrome) will abolish the lumen-positive gradient needed to drive magnesium reabsorption and, thus, result in magnesium wasting.

The potassium channel can be secondarily inhibited by the activation of the Ca2+/Mg2+ sensing receptor (CaSR). The CaSR binds both magnesium and calcium. This accounts for the observed magnesium wasting seen in the setting of hypercalcemia that augments activation of this receptor. If the positive transepithelial gradient is ultimately generated, the paracellular reabsorption of magnesium (and calcium) occurs passively, facilitated by the tight junction protein, paracellin-1 (claudin-16). The fact that both calcium and magnesium travel in parallel through the same channel in this part of the nephron explains why disturbances resulting in hypermagnesuria will simultaneously cause hypercalciuria. The mechanism(s) of magnesium reabsorption in the distal convoluted tubule (DCT) is less well understood. Although the distal nephron accounts for only approximately 5–10% of magnesium reabsorption, it does play an important role in determining the final urinary concentration of magnesium. Reabsorption is active and transcellular and is probably mediated by Mg2+ selective channels and a basolateral membrane Na+/Mg2+ exchanger.

Essentials of Diagnosis

• Serum magnesium level, <1.5 mg/dL.
• A normal serum magnesium level does not exclude the diagnosis of total body magnesium depletion.
• Hypomagnesemia is a relatively common disorder, occurring in 12% of hospitalized patients and in up to 60–65% of Intensive Care Unit (ICU) patients.
• Evidence suggests that the presence of hypomagnesemia in the ICU patient population is associated with increased morbidity and mortality.
• There are conflicting data regarding the benefits of preventing hypomagnesemia, possible preventive treatment strategies, and even the level of hypomagnesemia that should prompt supplementation.

Clinical Findings

Symptoms and Signs

The diversity of the cellular processes in which magnesium has been shown to take part is reflected by the diversity of symptoms attributed to magnesium deficiency (Table 8–1). Hypomagnesemia may be asymptomatic, particularly if it is mild and if it develops slowly. Severe hypomagnesemia, particularly if it develops rapidly, can be associated with signs and symptoms related to cardiovascular, neuromuscular, and central nervous system (CNS) dysfunction.

Magnesium regulates several cardiac ion channels including the calcium channel and outward potassium currents. Lowering myocardial cytosolic magnesium can lead to shortening of the action potential and an increased susceptibility to tachyarrhythmias, particularly of ventricular origin (including torsades de pointe, monomorphic ventricular tachycardia, and ventricular fibrillation). This is particularly true in acutely ill patients and in the setting of acute myocardial infarction, congestive heart failure, or after cardiopulmonary bypass surgery. Hypomagnesemia can magnify digitalis cardiotoxicity as both the cardiac glycoside and magnesium depletion reduce intracellular potassium by inhibition of the Na+-K+-ATPase. The EKG changes associated with hypomagnesemia include progressive widening of the QRS complex, prolongation of the PR interval, and abnormalities of T wave morphology.

Hypomagnesemia augments skeletal muscle contraction and delays muscle relaxation. Therefore, affected patients can develop signs of neuromuscular irritability including tremor, muscle twitching, Trousseau and Chvostek signs, and frank tetany. These signs may be exacerbated by a coexistent electrolyte abnormality such as hypocalcemia. Patients may also present with delirium, coma, or seizures.

Electrolyte disturbances associated with symptomatic magnesium depletion include hypokalemia and hypocalcemia, both of which can be refractory to treatment unless the underlying magnesium deficit is corrected. The hypokalemia that frequently accompanies hypomagnesemia may be due to (1) a direct effect of hypomagnesemia on potassium channels in the loop of Henle (and perhaps the cortical collecting tubule) due to impairment of the Mg-dependent Na+-K+-ATPase leading to renal potassium wasting; and (2) the underlying disorders (ie, diarrhea, diuretics) that simultaneously cause magnesium and potassium loss. The hypocalcemia that often accompanies severe magnesium depletion is due to the suppressive effect of hypomagnesemia on parathyroid secretion as well as skeletal resistance to parathyroid hormone (PTH). In addition, low plasma levels of calcitriol (1, 25-dihydroxyvitamin D) have been noted in hypomagnesemic states and can contribute to the fall in calcium concentrations.

Normomagnesemic magnesium depletion (total body magnesium depletion in normomagnesemic patients) should be considered in patients at risk for magnesium depletion who have clinical features consistent with magnesium depletion, such as unexplained hypocalcemia or hypokalemia.

Laboratory Findings

The terms hypomagnesemia and magnesium deficiency tend to be used interchangeably. However, because only a small fraction of magnesium is extracellular, the serum magnesium level is not a reliable way to assess total body magnesium depletion. The total body may be markedly depleted before the serum level drops. Hence, a normal magnesium level does not rule out the possibility of a magnesium deficit. Clues to the diagnosis of true magnesium depletion despite normal measured levels include persistent, unexplained hypocalcemia or hypokalemia, which is refractory to treatment or response to empiric treatment. The magnesium retention test, which measures urinary excretion of magnesium in response to an intravenous magnesium load, has also been used to assess total body magnesium status in patients suspected of having hypomagnesemia. When magnesium stores are deficient, more of the infused magnesium will be reabsorbed and, thus, less will be excreted in the urine. If less than 50% of the infused magnesium is recovered in the urine, magnesium deficiency is likely. However, this test is not in routine use as its utility is questionable and several conditions (ie, impaired renal function and renal magnesium wasting) and drugs can lead to invalid results.

If laboratory tests confirm hypomagnesemia, the next step is to distinguish between renal and extrarenal (gastrointestinal or miscellaneous) causes of magnesium wasting. A review of the clinical history can often provide this information (ie, chronic diarrhea causing excessive gastrointestinal magnesium losses). If the cause is not readily apparent, quantitative assessment of urinary magnesium excretion with a 24-hour urine collection or the calculation of the fractional excretion of magnesium (FeMg) on a random urine specimen can provide insight. In the setting of magnesium depletion, conservation of magnesium by normal kidneys can decrease the usual fractional excretion of magnesium from 3% (approximately 100 mg) to very low levels (ie, sometimes less than 0.5% or 12 mg/day). Therefore, demonstrating an inappropriately high rate of renal magnesium excretion in the setting of hypomagnesemia confirms the diagnosis of renal magnesium wasting. Table 8–2 summarizes the urine tests and the criteria used for renal magnesium wasting.

Etiology & Differential Diagnosis

There are multiple causes of hypomagnesemia (Table 8–3). When the cause is not obvious from the clinical history and examination, it is often helpful for the clinician to try to ascertain whether the cause is due to redistribution of extracellular magnesium into the intracellular compartment, a gastrointestinal source, urinary magnesium wasting, or “complex causes.”

Low measured serum magnesium is usually an indication of total body depletion. However, sometimes redistribution of extracellular magnesium into the intracellular compartment can lead to a decreased serum magnesium level. By itself, redistribution is an uncommon cause of significant hypomagnesemia, but it can unmask or exacerbate hypomagnesemia in patients with preexisting marginal stores. It can be encountered in a few settings. Sequestration of magnesium into the bone compartment may cause hypomagnesemia (in addition to profound hypocalcemia) in some patients with hyperparathyroidism and severe bone disease following parathyroidectomy. The sudden removal of excess PTH in this setting is believed to result in cessation of bone resorption with a continued high rate of bone formation. Insulin can also serve to drive magnesium (like potassium) into cells. Therefore, hypomagnesemia can be seen as part of the refeeding syndrome where overzealous administration of parenteral feeds to a malnourished patient results in a surge of endogenous insulin. Similarly, exogenous administration of insulin in the treatment of diabetic ketoacidosis can have the same effect.

Hypomagnesemia can result from chelation of the magnesium ion. This can be seen after massive blood transfusions (ie, >10 U/24 hours) due to the chelating effects of citrate, particularly when citrate clearance is diminished by renal or hepatic disease. It also may contribute to the hypomagnesemia seen following surgery where the postsurgical increase in circulating free fatty acids chelates magnesium. Hypomagnesemia may also accompany the acute hypocalcemia seen in acute pancreatitis and is presumably due to saponification of both cations in necrotic fat. Other causes of extracellular to intracellular magnesium redistribution include metabolic alkalosis and high catecholamine states.

Gastrointestinal Causes

If redistribution is ruled out and the urine findings are consistent with appropriate renal magnesium conservation, the gastrointestinal tract is the usual culprit. Induction of magnesium deficiency by inadequate dietary intake is not frequent because nearly all foods contain sufficient amounts of magnesium and renal conservation is so efficient. Nevertheless, magnesium deficiency of nutritional origin can be seen in a few clinical settings. It has been described in children with protein–calorie malnutrition (although usually in combination with gastrointestinal losses such as vomiting and diarrhea). It can be seen in hospitalized patients receiving only intravenous fluids or prolonged administration of magnesium-free parenteral nutrition. Therefore, addition of 4–12 mmol of magnesium per day to total parenteral nutrition (TPN) has been recommended to prevent hypomagnesemia. This is especially true in patients with marginal magnesium stores such as those with debilitating illnesses, anorexia, or with chronic alcohol use.

Although there is only a small amount of magnesium lost (approximately 40 mg/day) in intestinal secretions on a daily basis, enteric losses of magnesium can be substantial in patients with gastrointestinal fistulas, small bowel bypass surgery, or diarrheal illnesses. This is particularly true if the chronic diarrhea is associated with fat malabsorption syndromes in which free fatty acids within the intestinal lumen may combine with magnesium, forming unreabsorbable soaps. This saponification limits magnesium absorption. Decreased intestinal absorption can also be caused by a rare inherited disorder termed primary intestinal hypomagnesemia in which a mutation in the magnesium ion channel leads to impaired active transport in the intestine.

Renal Magnesium Wasting

If redistribution and gastrointestinal causes are excluded, and renal magnesium wasting is confirmed based on laboratory findings, hypomagnesemia is due to inappropriate renal losses of magnesium.

Diuretics are a frequent cause of renal magnesium wasting. Loop diuretics, which inhibit the Na+/K+/2Cl− cotransporter in the loop of Henle, lead to the loss of the positive transepithelial potential difference that drives paracellular divalent cation reabsorption, thereby resulting in both magnesuria and hypercalciuria. The etiology of magnesium wasting with chronic thiazide use is not fully understood. The degree of hypomagnesemia induced by the loop and thiazide diuretics is generally mild, in part because of the associated volume contraction that tends to increase proximal sodium, water, and magnesium reabsorption.

Numerous other drugs have also been shown to cause impairment in the renal tubular reabsorption of magnesium. Cisplatin, widely used as a chemotherapeutic agent for solid tumors, causes magnesium wasting in more than 50% of treated patients and the incidence increases with the cumulative dose. Renal magnesuria continues after the cessation of the drug for several months but can persist for years. The occurrence of magnesium wasting does not correlate with cisplatin-induced acute renal failure. Aminoglycosides such as gentamicin can induce magnesuria soon after the onset of therapy. The aminoglycoside-associated magnesuria is dose dependent, and is usually reversible upon withdrawal. Cyclosporin, pentamidine, and amphotericin B also cause renal magnesium wasting.

Since the bulk of the filtered magnesium is linked to sodium chloride reabsorption, it is not surprising that factors that increase urinary excretion of sodium will also promote the urinary excretion of magnesium. Mild hypomagnesemia can occur in states of sustained ECF volume expansion as might be seen in patients receiving large amounts of intravenous normal saline. It also accounts for the hypomagnesemia that can sometimes be observed in patients with primary hyperaldosteronism. In addition, any condition that gives rise to high urine flow rates can lead to magnesium wasting. High urine flow rates can contribute to hypomagnesemia in uncontrolled hyperglycemic states with glucosuria, the recovery polyuric phase of acute tubular necrosis, postobstructive diuresis, and after renal transplantation. In the latter conditions, the residual tubule reabsorptive defects that persist from the primary renal injury likely also play an important role in inducing renal magnesium wasting.

Magnesium handling can also be affected by other electrolytes. Hypercalcemia, hypokalemia, and phosphate depletion can all lead to magnesuria by inhibiting tubular magnesium reabsorption.

Several rare hereditary renal magnesium-wasting disorders have been described and the genetic basis for many of them has recently been characterized. They represent a heterogeneous group of disorders that can usually be distinguished from each other on the basis of the clinical presentation and biochemical profile that is summarized in Table 8–4. A helpful clue to the localization of the defect is the pattern of the calcium excretion in relation to the magnesium excretion, ie, the combination of hypermagnesuria and hypocalciuria is the finding pathognomic of disturbed DCT function. Demonstrating high urinary magnesium excretion in the absence of any other apparent cause establishes the diagnosis of these inherited disorders.

Complex Causes

Chronic alcoholics often have hypomagnesemia due to a combination of several factors including dietary deficiency, gastrointestinal losses (diarrhea, vomiting), and renal losses. The renal losses are a direct effect of the alcohol that can induce reversible tubular dysfunction leading to inappropriate magnesium excretion that can persist for weeks after abstinence. Alcoholics are also susceptible to acute pancreatitis, which in turn may contribute to the hypomagnesemia as a result of redistribution of magnesium as described above. Similarly, patients with insulin-dependent diabetes mellitus may have hypomagnesemia secondary to complex causes, particularly in the setting of diabetic ketoacidosis. Renal magnesium wasting accompanies the osmotic diuresis induced by hyperglycemia and rapid correction of hyperglycemia with insulin therapy drives magnesium into cells. Furthermore, magnesium deficiency may impair glucose disposal and aggravate insulin resistance.

Treatment

Whenever possible the underlying cause of the hypomagnesemia should be corrected. The route and rate of magnesium repletion depend on the severity of the clinical manifestations. Since plasma magnesium is the major regulator of magnesium reabsorption in the loop of Henle, an abrupt elevation in the plasma magnesium concentration following a bolus partially removes the stimulus for magnesium reabsorption resulting in up to half of a bolus infusion being lost in the urine. In addition, uptake of magnesium by cells is slow and repletion requires sustained correction of the hypomagnesemia.

Severe Hypomagnesemia

If hypomagnesium is severe (<1 mEq/L) or accompanied by symptoms such as cardiac arrhythmias, neuromuscular irritability, or seizures, parenteral magnesium therapy should be administered. Magnesium sulfate 1–2 g (8–16 mEq) can be given over 15 minutes. A continuous infusion should be given after the initial bolus, ie, with MgSO4 4–6 g/24 hours (32–48 mEq). Magnesium repletion should continue for at least 1–2 days after serum magnesium normalizes because the added extracellular magnesium equilibrates slowly with the intracellular compartment.

Adverse effects associated with intravenous magnesium repletion include facial flushing, loss of deep tendon reflexes (DTR), hypotension, atrioventricular block, and hypocalcemia. Since the major route of magnesium excretion is via the kidney, the above doses should be reduced and magnesium levels should be closely monitored in patients with a decreased glomerular filtration rate (GFR) who are receiving intravenous magnesium. If the underlying cause of the hypomagnesemia persists once the acute emergency has been corrected, oral magnesium replacement may be necessary.

Mild Hypomagnesemia

Given that significant wasting of magnesium occurs in the setting of rapid parenteral magnesium administration, treatment with oral magnesium salts is the more efficient way to replenish magnesium stores in patients who are asymptomatic or who require maintenance therapy due to chronic magnesium losses. The slower rise in the serum magnesium level that results from oral therapy provides a more favorable gradient for renal magnesium reabsorption. Sustained release preparations are preferable. There are two such preparations currently available, Slow-Mag containing magnesium chloride and Mag-Tab SR containing magnesium lactate. These orally administered magnesium preparations are given in divided doses to decrease their cathartic effect. Two to four tablets daily may be sufficient for mild asymptomatic disease whereas six to eight tablets daily may be required for severe magnesium depletion. Table 8–5 summarizes some of the commonly prescribed oral magnesium preparations.

If renal magnesium wasting persists despite high dose oral magnesium replacement (as in the inherited magnesium wasting disorders, cisplatin toxicity, etc.), addition of potassium-sparing diuretics such as amiloride may be beneficial. These drugs decrease magnesium excretion by increasing its reabsorption in the convoluted collecting tubule.

Prevention

Given the observed relationship between this electrolyte disorder and possible complications, it is important to recognize which patients are at increased risk of developing symptomatic hypomagnesemia and the clinical settings in which hypomagnesemia is frequently encountered. For example, patients in the ICU often have several etiologies of magnesium loss acting simultaneously, ie, poor nutrition, excessive gastrointestinal losses from diarrhea or vomiting, excessive renal losses from multiple medications such as diuretics and antibiotics, coexisting electrolyte and acid–base disturbances that exacerbate the losses, and therapeutic interventions that can redistribute magnesium. All these factors may be superimposed on a state of chronic magnesium depletion. In addition, many of these patients have underlying cardiac disease that may increase the risk of sudden death from hypomagnesemia. As such, these patients warrant more frequent monitoring of magnesium levels and systematic repletion if the disorder is discovered.

Essentials of Diagnosis

• Serum magnesium concentrations >2.5 mg/dL.
• Occurs almost exclusively in patients with renal insufficiency and is often iatrogenic.

General Considerations

Hypermagnesemia is a relatively infrequent laboratory finding and symptomatic hypermagnesemia is even less common. However, severe hypermagnesemia is a serious and potentially fatal condition. The kidney has a remarkable capacity to increase magnesium excretion in states of body magnesium excess. This explains why hypermagnesemia primarily occurs in two settings: impaired renal function and excess magnesium intake at a rate that exceeds the renal excretion capacity.

In patients with chronic kidney disease, the serum magnesium levels are generally well maintained until the GFR falls below 20 ml/minute because the remaining functioning nephrons are able to significantly increase the fractional excretion of magnesium. At lower levels of GFR (<10 mL/minute), mild to moderate levels of hypermagnesemia may be present (2.4–3.6 mg/dL). These patients are typically asymptomatic, but are particularly vulnerable to severe and potentially fatal, symptomatic hypermagnesemia when exposed to exogenous magnesium in the form of magnesium-containing bowel preparation regimens, antacids, or laxatives, even in the usual therapeutic doses. Similarly, patients with acute renal failure are susceptible to severe hypermagnesemia.

While much less common, there are situations in which hypermagnesemia can occur in the absence of significant renal insufficiency. Hypermagnesemia is induced deliberately in pregnant women with severe preeclampsia or eclampsia to decrease neuromuscular excitability. Such regimens, with large doses given rapidly and continuously (ie, Mg sulfate loading dose of 4–6 g, maintenance 2–3 g/hour continuous infusion), can overwhelm the renal excretory capacity, achieving serum magnesium levels in the range of 6–8.4 mg/dL, or higher. Severe hypermagnesemia in the setting of normal renal function has also occasionally been described with massive oral ingestions (ie, accidental poisoning with Epsom salts in children), in chronic laxative abusers, or in patients receiving large amounts of magnesium sulfate per rectum. An elevation of serum magnesium due to ingestion of magnesium-containing medications is more likely in the presence of gastrointestinal disorders that may enhance magnesium absorption. This phenomenon has been reported in patients with active ulcer disease, gastritis, inflammatory bowel disease, and intestinal obstruction. A geographically unique cause of severe hypermagnesemia has been described in Jordan due to near drowning in the Dead Sea. The magnesium concentration in the Dead Sea averages 400 mg/dL. Interestingly, since the Dead Sea also has very high levels of calcium, the resulting hypercalcemia may be somewhat protective against the cardiac toxicity associated with hypermagnesemia.

Mild hypermagnesemia, unrelated to renal insufficiency or disorders of the gastrointestinal tract, may be seen in the a variety of clinical settings. The causes of hypermagnesemia are listed in Table 8–6.

Clinical Findings

Symptoms and Signs

Signs and symptoms of hyermagnesemia are generally not apparent until the serum magnesium concentration exceeds 4 mg/dL. Concomitant hypocalcemia may exacerbate the symptoms of hypermagnesemia at any level. Neuromuscular and cardiovascular manifestations dominate the clinical picture. High levels of magnesium decrease transmission of neuromuscular messages by inhibiting acetylcholine at the neuromuscular endplate. This ultimately leads to decreased deep tendon reflexes, muscle weakness progressing to flaccid skeletal muscle paralysis, respiratory depression, and apnea. Urinary retention and intestinal ileus due to smooth muscle dysfunction may also occur. High levels of magnesium may also cause signs and symptoms of CNS depression including drowsiness and eventually coma. Fixed dilated pupils, induced by parasympathetic blockade, and masquerading as a central brain stem herniation syndrome, has been described. Parasympathetic blockade, vasodilation of vascular smooth muscle, and inhibition of norepinephrine release by sympathetic postganglionic nerves account for cutaneous flushing and hypotension. Hypermagnesemia also depresses the conduction system of the heart, which can manifest as lengthening of the QRS complex, PR or QT intervals, heart block, bradycardia, and eventually cardiac arrest. Hypocalcemia may be present at moderate levels of hypermagnesemia (>6 mg/dL, 5 mEq/L) due to the suppressive effects of high magnesium on PTH secretion. Hyperkalemia has been described in two hypermagnesemic patients. The mechanism is unclear, but may be related to decreased urinary excretion of potassium as a result of hypermagnesemia inducing blockade of renal potassium channels. Hypermagnesemia may decrease the anion gap, although this appears not to occur with infusion of magnesium sulfate, as retention of the anionic sulfate moiety counterbalances the unmeasured cation.

The magnesium levels at which the symptoms and signs of hypermagnesemia manifest are presented in Table 8–7.

Laboratory Findings

Elevated serum magnesium levels above 2.5 mg/dL are usually diagnostic. Hypocalcemia may be present at moderate levels of hypermagnesemia (>6 mg/dL, 5 mEq/L).

Treatment

The initial assessment should focus on identifying and discontinuing the source of exogenous magnesium. In patients with preserved renal function and mild manifestations of magnesium toxicity, cessation of exogenous magnesium administration may be the only treatment required. In the event of symptomatic, life-threatening hypermagnesemia associated with cardiovascular, neurologic, or respiratory complications, immediate administration of intravenous calcium can serve to temporarily antagonize the effects of magnesium until more definitive therapies can be initiated and take effect (Table 8–8). In patients who are not volume overloaded and in whom some renal function is preserved, volume expansion with intravenous normal saline may enhance renal magnesium excretion. The addition of loop diuretics can further augment the magnesuria by inhibiting magnesium reabsorption in the thick ascending limb of the loop of Henle. However, this therapy warrants monitoring of the calcium levels. It can result in hypercalciuria with hypocalcemia that can intensify the clinical signs of hypermagnesemia. If the aforementioned therapies are not feasible due to renal failure, hemodialysis or peritoneal dialysis against a low magnesium bath is the only way to effectively eliminate the excess body magnesium.

Prevention

Most cases of symptomatic hypermagnesemia can be prevented by anticipation. It is important to avoid magnesium-containing medications in patients with acute or chronic kidney disease as well as those with active gastrointestinal diseases. Patients receiving high doses of parenteral magnesium should be closely monitored.