eMedicine Specialties > Nephrology > Acid-Base, Fluid, and Electrolyte Disorders
Hypermagnesemia
Updated: Apr 8, 2009
Introduction
Hypermagnesemia is an uncommon clinical finding, and symptomatic hypermagnesemia is even less common. This disorder 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.
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 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.1 Relatively little is known about cellular magnesium transport mechanisms.2
The most common cause of hypermagnesemia is renal failure. Other causes include the following3,4 :
- 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. In patients undergoing regular dialysis, the serum magnesium level directly relates to the dialysate magnesium concentration.5
In patients with acute renal failure, hypermagnesemia usually presents during the oliguric phase; the serum magnesium level returns to normal during the diuretic 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, laxatives,6 rectal enemas). Hypermagnesemia can develop after treatment of drug overdoses with magnesium-containing cathartics,7 and it also occurs in patients taking magnesium-containing medications for therapeutic purposes8,9 ; however, most of these patients have normal renal function. If the patient does not ingest a large amount of magnesium but has a gastrointestinal disorder (eg, gastritis, colitis, gastric dilation), absorption may increase.10,11 In any case, monitoring serum magnesium levels in patients taking magnesium-containing medications is prudent.
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.4
In the treatment of eclampsia, hypermagnesemia is induced deliberately and sometimes can be symptomatic.8,12,13 Occasionally, hypermagnesemia also can occur in the newborn infant.14 Maternal magnesium therapy can cause neurobehavioral disorders in the newborn.15
Magnesium-containing phosphorus binders are rarely used in end-stage renal disease patients16 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.17 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,18 resulting in increased magnesium reabsorption in the loop of Henle.
Hypothyroidism, adrenal insufficiency, milk-alkali syndrome3,4 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 hemorrhage19,20 ; however, significant hypermagnesemia has not been reported in these settings.
Effects of Hypermagnesemia
Symptoms of hypermagnesemia usually are not apparent unless the serum magnesium level is greater than 2 mmol/L. Concomitant hypocalcemia, hyperkalemia, or uremia exaggerate the symptoms of hypermagnesemia at any given level.
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.21
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.21 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 results from a decrease in the secretion of parathyroid hormone (PTH) or from end-organ resistance to PTH.22 Paralytic ileus develops from smooth-muscle paralysis,10 and mothers being treated with magnesium for preterm labor suppression are at risk.23
Hypermagnesemia may interfere with blood clotting through interference with platelet adhesiveness, thrombin generation time, and clotting time.
Nonspecific symptoms
These symptoms include nausea, vomiting, and cutaneous flushing.
Medication
Prevention of hypermagnesemia is usually possible. Anticipate hypermagnesemia in patients who are receiving magnesium treatment, especially those with reduced renal function. Initially, withdraw magnesium therapy, which often is enough to correct mild to moderate hypermagnesemia.
In patients with symptomatic hypermagnesemia that is causing cardiac effects or respiratory distress, antagonize the effects by infusing calcium gluconate. Calcium antagonizes the toxic effect of magnesium, and these ions electrically oppose each other at their sites of action. This treatment usually leads to immediate symptomatic improvement.
Diuretics
Agents that promote magnesium excretion are effective in treating hypermagnesemia.
Furosemide (Lasix)
May promote excretion of magnesium. Increases excretion of water by interfering with chloride-binding cotransport system, which, in turn, inhibits sodium and chloride reabsorption in ascending loop of Henle and distal renal tubule.
Adult
Suggested dosing: 20-80 mg/d PO/IV/IM; titrate up to 600 mg/d for severe edematous states
Pediatric
Suggested PO dosing: 1-2 mg/kg/dose; not to exceed 6 mg/kg/dose; do not administer more often than q6h
Suggested IV/IM dosing: 1 mg/kg slowly under close supervision; not to exceed 6 mg/kg
Metformin decreases concentrations; interferes with hypoglycemic effect of antidiabetic agents and antagonizes muscle-relaxing effect of tubocurarine; auditory toxicity appears to be increased with coadministration of aminoglycosides; hearing loss of varying degrees may occur; anticoagulant activity of warfarin may be enhanced when taken concurrently; increased plasma lithium levels and toxicity are possible when taken concurrently
Documented hypersensitivity; hepatic coma, anuria, and state of severe electrolyte depletion
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
Perform frequent serum electrolyte, carbon dioxide, glucose, creatinine, uric acid, calcium, and BUN determinations during first few months of therapy and periodically thereafter
Calcium salts
Calcium may moderate nerve and muscle performance in hypermagnesemia.
Calcium gluconate (Kalcinate)
Calcium directly antagonizes neuromuscular and cardiovascular effects of magnesium. Use for patients with symptomatic hypermagnesemia that is causing cardiac effects or respiratory distress.
Adult
Suggested dosing: 100-300 mg elemental calcium IV diluted in 150 mL D5W over 10 min; initial rate of infusion should be 0.3-2 mg of elemental calcium/kg/h
Pediatric
Suggested dosing: 2 mg/kg of elemental calcium IV (about 20 mg/kg of calcium gluconate 10%)
May decrease effects of tetracyclines, atenolol, salicylates, iron salts, and fluoroquinolones; antagonizes effects of verapamil; high intake of dietary fiber may decrease calcium absorption and levels
Renal calculi, hypercalcemia, hypophosphatemia, renal or cardiac disease, digitalis toxicity
Pregnancy
B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals
Precautions
Caution in patients on digoxin or with respiratory failure, acidosis, or severe hyperphosphatemia
Antidiabetic agents
Agents that shift magnesium ions into cells are helpful in treating hypermagnesemia.
Glucose and insulin
May help promote magnesium entry into cells. Glucose should be administered with insulin to prevent hypoglycemia. Monitor blood sugar levels frequently.
Adult
Suggested dosing: 10 U IV and 50 mL D50W bolus or 500 mL D10W over 1 h
Pediatric
Suggested dosing: 0.5-1 g/kg IV followed by 1 U of regular insulin per 3 g glucose
Medications that may decrease hypoglycemic effects of insulin include acetazolamide, AIDS antivirals, asparaginase, phenytoin, nicotine, isoniazid, diltiazem, diuretics, corticosteroids, thiazide diuretics, thyroid estrogens, ethacrynic acid, calcitonin, oral contraceptives, diazoxide, dobutamine, phenothiazines, cyclophosphamide, dextrothyroxine, lithium carbonate, epinephrine, morphine sulfate, and niacin; medications that may increase hypoglycemic effects of insulin include calcium, ACE inhibitors, alcohol, tetracyclines, beta-blockers, lithium carbonate, anabolic steroids, pyridoxine, salicylates, MAOIs, mebendazole, sulfonamides, phenylbutazone, chloroquine, clofibrate, fenfluramine, guanethidine, octreotide, pentamidine, and sulfinpyrazone
Documented hypersensitivity, hypoglycemia
Pregnancy
B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals
Precautions
Hyperthyroidism may increase renal clearance of insulin, and more insulin may be required to treat hyperkalemia; hypothyroidism may delay insulin turnover, requiring less insulin to treat hyperkalemia; monitor glucose carefully; dose adjustments of insulin may be necessary in patients diagnosed with renal and hepatic dysfunction
Diagnosis and Summary
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.24 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.
Keywords
hypermagnesemia, magnesium, kidney failure, kidney disease, ESRD, calcium magnesium, renal failure, end stage renal disease, magnesium laxative, serum magnesium, end stage kidney disease, excess magnesium, magnesium toxicity, magnesium overdose, magnesium overload, magnesium excess, lithium therapy, hypothyroidism, Addison disease, familial hypocalciuric hypercalcemia, milk-alkali syndrome, milk alkali syndrome
The primary author would like to thank to Drs. Gurvinder Suri and Mohit Ahuja, Renal Fellows at the University of Mississippi Medical Center - Nephrology Division, for their valuable peer review.
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References
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Further Reading
Related eMedicine topics:
Hypermagnesemia [Emergency Medicine]
Hypermagnesemia [Pediatrics: General Medicine]
Hypomagnesemia [Emergency Medicine]
Hypomagnesemia [Pediatrics: General Medicine]
Milk-Alkali Syndrome
Renal Failure, Chronic and Dialysis Complications
Clinical guidelines:
The management of severe pre-eclampsia/eclampsia. Royal College of Obstetricians and Gynaecologists - Medical Specialty Society. 2006 Mar. 11 pages. NGC:005033
Clinical trials:
Intravenous Magnesium Sulfate in Aneurysmal Subarachnoid Haemorrhage (IMASH)
Labetalol Versus MgSO4 for the Prevention of Eclampsia Trial
Treatment Approaches for Preeclampsia in Low-Resource Settings
Keywords
hypermagnesemia, magnesium, kidney failure, kidney disease, ESRD, calcium magnesium, renal failure, end stage renal disease, magnesium laxative, serum magnesium, end stage kidney disease, excess magnesium, magnesium toxicity, magnesium overdose, magnesium overload, magnesium excess, lithium therapy, hypothyroidism, Addison disease, familial hypocalciuric hypercalcemia, milk-alkali syndrome, milk alkali syndrome
