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Hypermagnesemia (>2.5 mEq/L) occurs most commonly from iatrogenic causes and excessive use of antacids or laxatives. It is rare in clinical medicine, because magnesium is relatively poorly absorbed from the gastrointestinal tract and renal elimination of excess magnesium is extremely rapid (within 4 to 8 hours of a magnesium load). Because elimination is directly related to the glomerular filtration rate, patients with kidney failure are at increased risk of developing hypermagnesemia. Signs and symptoms are directly related to the blood level and include alterations in the nervous, cardiovascular, respiratory, and genitourinary systems.
Magnesium depresses the central nervous system and, in the early 1900s, was used effectively as a general anesthetic. Magnesium penetrates the blood-brain barrier poorly, however, and its level in the cerebrospinal fluid is well controlled by an active transport mechanism.[54] Magnesium probably does not have major anticonvulsant properties unless the convulsions result from magnesium deficiency.[54] It is believed that the anticonvulsant activity of magnesium is related to its powerful cerebral
| Causes | Mechanisms |
|---|---|
| Primary nutritional disturbances | Inadequate intake; total parenteral nutrition; refeeding syndrome |
| Gastrointestinal disorders | Specific absorptive defects; malabsorption syndromes; prolonged diarrhea; prolonged nasogastric suction; pancreatitis |
| Endocrine disorders | Hyperparathyroidism; hypoparathyroidism; hyperthyroidism; primary hyperaldosteronism; Bartter's syndrome; diabetic or alcoholic ketoacidosis; administration of epinephrine; syndrome of inappropriate antidiuretic hormone (SIADH); hungry bone syndrome after parathyroidectomy |
| Chronic alcoholism, alcoholic withdrawal, increased renal excretion | Ethanol ingestion; idiopathic; after renal transplantation; drugs such as cisplatin, aminoglycoside, amphotericin B, diuretics, pentamidine, and theophylline; recovery phase of acute tubular necrosis; colony-stimulating factor therapy |
| Adapted from Potts JT: Diseases of the parathyroid gland and other hyper- and hypocalcemic disorders. In Isselbacher KJ, Braunwald E, Wilson JD, et al (eds): Harrison's Principles of Internal Medicine, 13th ed. New York, McGraw-Hill, 1995, p 2188. | |
In the peripheral nervous system, magnesium interferes with the release of neurotransmitters at all synaptic junctions and potentiates the action of local anesthetics.[54] At the neuromuscular junction, magnesium concentrations of 5 mmol/L cause significant presynaptic neuromuscular blockade and enhance the action of the nondepolarizing muscle relaxants.[54] It may precipitate severe muscle weakness in patients with Eaton-Lambert syndrome or myasthenia gravis.[54] Magnesium prolongs the action of depolarizing relaxants (e.g., succinylcholine); administration before the use of succinylcholine prevents the release of potassium provoked by the relaxant.
In the cardiovascular system, magnesium produces vasodilation by direct action on blood vessels and by interfering with a wide range of vasoconstrictor substances. It also reduces peripheral vascular tone by sympathetic blockade and inhibition of catecholamine release.[54] In the isolated heart, increased concentrations of extracellular magnesium ion markedly depress contractile force. Decreased myocardial performance has been demonstrated after a bolus of 2.5 g of magnesium sulfate. Reports have been published of severe myocardial depression with combinations of magnesium and diltiazem. In the isolated heart, magnesium produces bradycardia, but in the intact subject, the inhibition of vagal acetylcholine release produced by magnesium overrides the intrinsic slowing, and a mild tachycardia occurs. Magnesium is effective in treating a variety of arrhythmias, including ventricular arrhythmias, torsade de pointes, arrhythmias associated with epinephrine administration, and digitalis-associated arrhythmias. It is also efficacious in certain arrhythmias induced by hypokalemia, alcoholism, and myocardial infarction and may protect against bupivacaine-induced arrhythmias.
In the respiratory system, magnesium has no effect on central respiratory drive, and its only respiratory depressant effect is caused by the neuromuscular block that it produces. It is an effective bronchodilator and has been successfully used in severe asthma. Because magnesium inhibits catecholamine-induced arrhythmias, the possibility that magnesium may increase the effectiveness of β-agonists in the management of asthma is being evaluated in clinical trials.
In the genitourinary system, magnesium is a powerful tocolytic and has been used for many years in the management of premature labor. Magnesium is also used in obstetrics to prevent preeclamptic patients from developing seizures. Animal studies have shown that magnesium suppresses electroencephalographic spike activity. Therapeutic magnesium levels range from 5.0 to 7.0 mg/dL when administered for preeclampsia. When levels exceed 15 to 20 mg/dL, respiratory depression can become profound. In the kidney, magnesium is a renal vasodilator and a diuretic.
Symptoms and electrocardiographic changes of hypermagnesemia correspond to serum levels; depressed cardiac conduction, widened QRS complexes, prolonged P-Q intervals, and nausea appear between 5 and 10 mg/dL. Sedation, hypoventilation, decreased deep tendon reflexes, and muscle weakness appear at levels between 20 and 34 mg/dL, with hypotension, bradycardia, and diffuse vasodilation occurring at levels of 24 to 48 mg/dL. Areflexia, coma, and respiratory paralysis occur at 48 to 72 mg/dL. For these reasons, all patients being treated with magnesium therapy are clinically observed for magnesium intoxication.
Elimination of magnesium involves fluid loading followed by or with concomitant diuresis. Definitive therapy involves dialysis. Temporary reversal of the effects of magnesium can be managed with calcium therapy. Because hypermagnesemia potentiates the effects of depolarizing and nondepolarizing muscle relaxants, these agents must be carefully titrated in conjunction with appropriate assessment of neuromuscular blockade.[55]
The deleterious effects of magnesium deficiency are well recognized, and most critical care units monitor magnesium levels. In coronary care units, several studies have shown that the infusion of magnesium sulfate can reduce the incidence and severity of cardiac arrhythmias associated with myocardial infarction. Numerous reports in the literature describe the bronchodilator effect of magnesium and its successful use in the management of asthma. Magnesium may decrease the incidence of adrenergically mediated arrhythmias without interfering
In summary, magnesium has several important pharmacologic actions. Its route of elimination is renal. Magnesium should be regarded as a cardiovascular drug, first and foremost, with calcium antagonistic and anti-adrenergic properties that may be accompanied by minimal myocardial depression.[54]
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