Magnesium and potassium supplementation in the prevention of diabetic vascular disease.

Vascular disease underlies many of the complications of diabetes and includes coronary, cerebral, renal, peripheral and retinal vascular abnormalities. Magnesium (Mg) and potassium (K) deficiencies occur frequently in diabetic patients. Because of the vasoconstrictive effects of hypomagnesemia and hypokalemia and the adverse effects of Mg and K deficiency on carbohydrate metabolism we hypothesize that routine Mg and K supplementation of all hypomagnesemic diabetics will ameliorate or prevent the ravages of diabetic vascular disease.

Electrolyte & water metabolism in sports activities.

Few studies in water and electrolyte metabolism during sports activities have directed attention to magnesium. Addition of magnesium to sports beverages in appropriate concentrations appears to be safe. This article considers the potential role and availability of magnesium in fluid repletion during sports activities.

Clinical disorders of magnesium metabolism.

Normal Mg metabolism has been reviewed. The most expeditious method of identifying disorders of Mg deficiency or excess is to order a serum Mg determination. In our opinion, routine serum Mg would significantly enhance the clinician's ability to identify disorders of Mg metabolism. Refractory K repletion can be avoided by identifying co-existing hypomagnesemia in hypokalemic patients; as a result, prompting the clinician to institute simultaneous repletion of Mg as well as K. While oral Mg is the preferred route of repletion in critically ill patients, intravenous administration of Mg is recommended. Refractory hypotension, mental obtundation, and respiratory arrest occur with significant hypermagnesemia. Hemodialysis is recommended for treatment of symptomatic hypermagnesemia.

Significance of magnesium in congestive heart failure.

Electrolyte balance has been regarded as a factor important to cardiovascular stability, particularly in congestive heart failure. Among the common electrolytes, the significance of magnesium has been debated because of difficulty in accurate measurement and other associated factors, including other electrolyte abnormalities. The serum magnesium level represents < 1% of total body stores and does not reflect total-body magnesium concentration, a clinical situation very similar to that of serum potassium. Magnesium is important as a cofactor in several enzymatic reactions contributing to stable cardiovascular hemodynamics and electrophysiologic functioning. Its deficiency is common and can be associated with risk factors and complications of heart failure. Typical therapy for heart failure (digoxin, diuretic agents, and ACE inhibitors) are influenced by or associated with significant alteration in magnesium balance. Magnesium therapy, both for deficiency replacement and in higher pharmacologic doses, has been beneficial in improving hemodynamics and in treating arrhythmias. Magnesium toxicity rarely occurs except in patients with renal dysfunction. In conclusion, the intricate role of magnesium on a biochemical and cellular level in cardiac cells is crucial in maintaining stable cardiovascular hemodynamics and electrophysiologic function. In patients with congestive heart failure, the presence of adequate total-body magnesium stores serve as an important prognostic indicator because of an amelioration of arrhythmias, digitalis toxicity, and hemodynamic abnormalities.

Metabolic correlates of theophylline therapy: a concentration-related phenomenon.

OBJECTIVE: To determine the relationship of serum theophylline concentration with electrolyte and glucose abnormalities across a broad range of theophylline concentrations. DESIGN: Retrospective review of a computerized laboratory database between June 1, 1984 and June 1, 1986. SETTING: A midwestern university medical center. PATIENTS: Eight hundred sixty-nine patients with serum theophylline concentrations of > 5.5 mumol/L and a random unmatched sample (control group) of 350 in- and outpatient adults and children with no history of reactive airways disease or theophylline exposure. RESULTS: Patients with measurable theophylline had a higher risk of hypokalemia, hyponatremia, hyperglycemia, hypophosphatemia, and hypomagnesemia compared with the unexposed control group. Unadjusted odds ratios (OR) were: (1) hypokalemia OR = 4.2 (95 percent CI 2.2 to 7.9); (2) hyponatremia OR = 5.4 (95 percent CI 2.0 to 12.9); (3) hypomagnesemia OR = 1.6 (95 percent CI 1.0 to 2.5); (4) hyperglycemia OR = 2.3 (95 percent CI 1.7 to 3.0); and (5) hypophosphatemia OR = 2.7 (95 percent CI 1.2 to 5.3). A linear concentration-response relationship was documented between serum theophylline concentration and all metabolic disturbances. CONCLUSIONS: Measurable theophylline was associated with increased risk for glucose and electrolyte abnormalities in a concentration-related fashion across a broad range of theophylline concentrations from 5.5 to > or = 110 mumol/L.

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 appear 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.

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 essential to 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.

Refractory potassium repletion. A consequence of magnesium deficiency.

Experimental and clinical observations support the view that uncorrected magnesium (Mg) deficiency impairs repletion of cellular potassium (K). This is consistent with the observed close association between K and Mg depletion. Concomitant Mg deficiency in K-depleted patients ranges from 38% to 42%. Refractory K repletion due to unrecognized concurrent Mg deficiency can be clinically perplexing. Refractory K repletion as a consequence of Mg deficiency may be operative in patients with congestive failure, digitalis toxicity, cisplatin therapy, and in patients receiving potent loop diuretics. Therefore, we recommend that: (1) serum Mg be routinely assessed in any patients in whom serum electrolytes are necessary for clinical management and (2) until serum Mg is routinely performed consideration should be given to treating hypokalemic patients with both Mg as well as K to avoid the problem of refractory K repletion due to coexisting Mg deficiency.

Acceptability and effect of carbohydrate-electrolyte solutions on electrolyte homeostasis during field training.

Two lemon-lime flavored 2.5% carbohydrate-electrolyte solutions (CE1 supplemented with Na+, K+, and Mg+; and CE2 supplemented with NA+) were compared to plain water (water) and lemon-lime flavored water placebo (placebo) to evaluate their acceptability and consumption during 8 days of field training in hot weather. Acceptability ratings and consumption of CE2 and the flavored water placebo were similar and greater, respectively, than those for CE1. Average Na+ and K+ intakes, and serum electrolytes levels, were not affected during the 8-day trial. If food intake is adequate, consumption of carbohydrate-electrolyte solutions is apparently unnecessary to maintain electrolyte homeostasis.

Health screening in elderly Oklahomans.

A total of 550 males and 457 females in their 60s and 70s were screened for height and weight, blood pressure, glucose, cholesterol, and hemoglobin. Statistical analysis was performed using SAS software. Male values were abnormal for all screening parameters except for cholesterol. Statistically significant lower hemoglobin in males suggests that blood loss may be a problem, and in males increases in body weight and glucose may herald a higher frequency of cardiovascular disease. Control of blood pressure, weight reduction, decreased consumption of fat and salt, and regular exercise may be the health imperatives in this group of elderly Oklahomans.

Incidence of hypohydration when consuming carbohydrate-electrolyte solutions during field training.

Carbohydrate-electrolyte solutions (CE1, CE2) were evaluated for their ability to reduce the incidence of hypohydration during field training in hot weather (max Tamb = 88 degrees-100 degrees F). Hydration status was monitored twice daily in Army reservists who consumed ad libitum CE1, or CE2, or water, or a flavored water placebo. The water group had the highest percentage incidence of urine specific gravity greater than or equal to 1.030 (22%), whereas CE2 and flavored water placebo groups had the lowest (6% and 8%, respectively). Average total fluid intake was greatest in CE2 and lowest in CE1. CE2 and flavored water placebo were more effective than CE1 and water in reducing the overall incidence of hypohydration during this field exercise.

Carbohydrate-electrolyte solutions during field training: an overview.

The rationale and methods of evaluating two carbohydrate-electrolyte solutions at a field training exercise in hot weather are presented in this overview. The carbohydrate-electrolyte solutions were formulated to produce a multipurpose replacement beverage which could satisfy diverse requirements of troops working in hot climates. Several uses of these beverages include replacement of electrolytes and fluid while in Mission Oriented Protective Posture IV, fluid replacement for mild heat casualties, and oral rehydration therapy for treatment of diarrheal losses.

Routine serum magnesium determination: a contemporary clinical imperative.

Identification of hypomagnesaemia or hypermagnesaemia is presently the most expeditious method of clinically identifying perturbations in Mg metabolism. Clinicians may overlook as much as 90% of clinical hypomagnesaemia and hypermagnesaemia when serum Mg is determined on order versus on a routine basis. Routine serum Mg determination will facilitate management of digitalis toxicity in patients who are not currently identified as being hypomagnesaemic as well as preventing the occurrence of refractory K repletion. In our opinion routine serum Mg determination represents a clinical need which has not been addressed to date.

Frequency of hypomagnesemia and hypermagnesemia. Requested vs routine.

This study was designed to assess the effectiveness of identifying serum magnesium abnormalities by comparing physician-initiated requests for this analyte with routine magnesium determinations. Because magnesium abnormalities frequently accompany other electrolyte abnormalities, we measured magnesium in 1033 serum specimens submitted for electrolyte analyses. Physician-initiated requests for magnesium measurements were received for 81 (7.4%) of these specimens. Serum magnesium abnormalities were identified in 546 of the 1033 specimens (hypomagnesemia [less than 0.74 mmol/L], 487; hypermagnesemia [greater than 0.99 mmol/L], 59). Only 10% of the hypomagnesemic patients (48/487) and 13% of the hypermagnesemic patients (7/59) were identified by physician-initiated requests for this analyte. Fifty-three patients were both hypomagnesemic/hypokalemic and 30 patients were both hypomagnesemic/hyponatremic, but only 8 (15%) and 3 (10%), respectively, had physician-initiated requests for magnesium. Because magnesium abnormalities in significant numbers of patients are not being detected, we recommend routine measurement of this analyte when analyses of electrolytes are required for the care of patients.

Refractory potassium repletion due to cisplatin-induced magnesium depletion.

Cisplatin is a common cause of hypomagnesemia and hypokalemia due to renal magnesium (Mg) and potassium (K) losses. Magnesium plays an important role in the maintenance of intracellular K. An unrecognized and untreated Mg depletion can lead to a refractory K repletion. We describe two patients with hypomagnesemia-associated refractory hypokalemia following cisplatin following cisplatin therapy. Potassium supplementation failed to replace the K deficit. Profound hypokalemia persisted until hypomagnesemia was recognized and corrected. In neither patient was the concurrent hypomagnesemia recognized until the 11th and 9th hospital days. These two cases demonstrated the association of a refractory K repletion and an Mg deficiency. Thus, both serum K ion and Mg levels should routinely be assessed in patients who require cisplatin therapy.