Robert Whang

Magnesium Homeostasis and Clinical Disorders of Magnesium Deficiency

OBJECTIVE: To survey the causes of clinical hypomagnesemia and Mg deficiency. The relationship of hypomagnesemia to digitalis toxicity, congestive heart failure, arrhythmias, and acute myocardial infarction is discussed, as is the clinical interrelationship of Mg and K concentrations, the principal intracellular cations. DATA SOURCES: A MEDLINE search and retrieval was used to identify relevant references. STUDY SELECTION: Clinical reports, as well as studies, were selected for this review. DATA EXTRACTION: There were very few placebo-controlled clinical studies. Clinical observations were related primarily to compilation of series in which Mg was administered and clinical results reported. In addition, conclusions derived from review articles on the subject of clinical Mg depletion were used. DATA SYNTHESIS: Clinical diagnosis of Mg deficiency is ascertained most expeditiously by estimating serum Mg concentrations. Although available on order by physicians, the lack of routine serum Mg analysis as part of the “electrolyte panel” impedes the diagnosis of clinical Mg deficiency. Renal loss of Mg resulting from the widespread use of loop diuretics is responsible for significant numbers of patients with Mg deficiency and hypomagnesemia. Life threatening cardiac arrhythmias and seizures represent the most serious manifestations of clinical hypomagnesemia and Mg depletion. In the most critically ill patients, treatment with intravenous Mg is recommended. Oral repletion of Mg is reserved for the less critically ill hospitalized patients and ambulatory patients. Close attention must be paid to optimizing K replenishment in hypokalemic patients by concurrent treatment of any accompanying hypomagnesemia to avoid the problem of refractory K repletion. CONCLUSIONS: Hypomagnesemia is one of the most frequent serum electrolyte abnormalities in current clinical practice. Routine inclusion of serum Mg analysis in the electrolyte panel will enhance the clinical recognition and treatment of hypomagnesemic Mg-depleted patients. Failure to respond to treatment of recurrent ventricular tachycardia/fibrillation to usual antiarrhythmic therapy in patients with acute myocardial infarction, idiopathic dilated cardiomyopathy, and congestive heart failure should alert the clinician to consider administering intravenous Mg. Repair of coexisting hypomagnesemia in hypokalemic patients is essentialto avoid the problem of refractory K repletion caused by coexisting Mg depletion. More controlled clinical studies of Mg deficiency are necessary to ascertain the cost-effectiveness of Mg replacement therapy.

Effect of Magnesium Deficiency on Cardiac and Skeletal Muscle Potassium During Dietary Potassium Restriction

Summary The influence of coexisting Mg deficiency on cardiac and skeletal muscle K depletion was investigated. Rats were subject to either a K deficiency or K plus Mg deficiency regimen. It is concluded that: 1. K deficiency accompanied by coexisting Mg deficiency results in accelerated deficit of K in both cardiac and skeletal muscle when contrasted to K deficiency alone. 2. In contrast to skeletal muscle, cardiac muscle was relatively resistant to K loss during K and Mg depletion. The authors thank Miss Joan Rambush for assistance in the preparation of this manuscript.

Intravenous Magnesium Therapy in Acute Myocardial Infarction

OBJECTIVE: To review the methods and summarize the findings of clinical trials evaluating the use of intravenous magnesium (Mg2+) in acute myocardial infarction (AMI); to discuss serum Mg2+ in AMI and the potential mechanisms by which intravenous Mg2+ may be effective. Tables are used extensively to provide detailed information about the various trials. DATA SOURCES: A MEDLINE search was used to identify pertinent literature. Additional references were obtained from the articles retrieved from that search. STUDY SELECTION: Studies randomized and/or placebo-controlled were selected for review. Additional relevant citations were used in the introductory material and discussion. DATA EXTRACTION: There were surprisingly few large, placebo-controlled trials. All clinical trials available at the time of publication were reviewed. Only eight trials enrolled sufficient numbers of patients and/or were of adequate design to make meaningful interpretations. The description of the methods and results of these articles are the basis of this review. Although additional controlled studies with more subjects are needed, the results to date form a foundation from which to make inferences regarding the utility of this therapeutic modality. DATA SYNTHESIS: Intravenous Mg2+ has been demonstrated, albeit inconclusively, to reduce immediate and long-term morbidity and mortality when given in the immediate postinfarction period. Six of the eight controlled trials discussed report a decrease in the overall incidence of arrhythmia or in the frequency of arrhythmia requiring treatment. Four of the eight reported statistical significance. Five of the six trials evaluating mortality reported a decrease in the mortality rate from intravenous Mg2+ administered post-MI. Four of the five reported statistical significance. The favorable effect of intravenous Mg2+ on the mortality rate appears to occur in the first 30 days post-MI and is maintained through at least one year. The effects appear to be independent of concurrent therapy and do not appeart to relate to baseline serum Mg2+ concentrations. Intravenous Mg2+ appears to be safe and well tolerated. Flushing, hypotension, and atrioventricular (AV) node conduction abnormalities occur on occasion and seem related to the rate of administration. The exact dosage in this setting remains to be determined. CONCLUSIONS: Additional, well-designed, multicenter, controlled trials evaluating intravenous Mg2+ in AMI are needed. The pending Fourth International Study of Infarct Survival, with an anticipated 400 000 subjects, should clarify a number of unresolved issues regarding this therapy. Based on the information available to date, however, intravenous Mg2+ as a significant therapeutic modality for AMI shows promise. Pending further investigation, however, it should be avoided in patients with significant sinoatrial or AV conduction disturbances.