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Objectives: The aims of this study were to evaluate the safety and efficacy of magnesium replacement therapy and to determine its effect on potassium retention in hypokalemic, critically ill patients.

Design: A prospective, double-blind, randomized, placebo-controlled trial.

Setting: A surgical intensive care unit (ICU).

Patients: A total of 32 adult surgical ICU patients were admitted to the study on the basis of documented hypokalemia (potassium of less than 3.5 mmol/L) within the 24-hr period before entering the study. Patients were randomized to receive either placebo (n equals 15) or magnesium sulfate (n equals 17). One patient from each group was excluded from the study due to failure to complete the full series of doses.

Interventions: Patients received a "test dose" of either magnesium sulfate (2 g, 8 mmol) or placebo (5% dextrose in water) infused over 30 mins every 6 hrs for eight doses. The next scheduled test dose was held if hypermagnesemia (magnesium of more than 2.8 mg/dL [more than 1.15 mmol/L]) was documented at any time during the study. Routine replacements of potassium and magnesium continued during the duration of the study, when clinically indicated, for serum potassium concentrations of 3.5 mmol/L or serum magnesium concentrations of less than 1.8 mg/dL (less than 0.74 mmol/L).

Measurements and Main Results: Age, weight, and Acute Physiology and Chronic Health Evaluation II scores were recorded on entry into the study. Just before administration of each test dose, blood was drawn for magnesium and potassium, bicarbonate, pH, and glucose determinations, and an aliquot of the preceding 6 hrs urine collection was sent for magnesium and potassium determinations. Serum calcium, phosphate, urea nitrogen, and creatinine concentrations were measured daily. The amounts of magnesium and potassium administered via parenteral nutrition, tube feeding, and replacement infusions were calculated for each 6-hr interval. The amounts of magnesium and potassium excreted in the urine were similarly assessed.

The groups showed no differences with regard to age, weight, Acute Physiology and Chronic Health Evaluation II scores, or initial serum magnesium concentration.Initial potassium, bicarbonate, pH, calcium, phosphate, glucose, blood urea nitrogen, and creatinine values were not different between groups. Patients receiving magnesium sulfate showed a statistically significant increase in serum magnesium concentration at 6 hrs when compared with placebo, as well as with itself at time 0 (p less than .0001), a difference maintained throughout the study. Compared with the placebo group, the total amount of elemental magnesium administered was significantly greater in the treatment group (1603 plus minus 124 vs. 752 plus minus 215 mg [65.7 plus minus 5.8 vs. 30.8 plus minus 8.8 mmol], p less than .0001), as was urine magnesium excretion (1000 plus minus 156 vs. 541 plus minus 68 mg [41.0 plus minus 6.4 vs. 22.2 plus minus 2.8 mmol] p less than .0001). However, the net magnesium balance (total magnesium in - total urine magnesium) was signficantly more positive in the treatment group (612 plus minus 180 vs. 216 plus minus 217 mg [25.1 plus minus 7.4 vs. 8.9 plus minus 8.9 mmol], p less than .005). The treatment and control groups had the same serum potassium concentrations and did not receive different amounts of potassium (245 plus minus 39 vs. 344 plus minus 45 mmol, respectively, p equals .06), although the treatment group required less potassium replacement/6 hrs by 30 hrs compared with itself at time 0 (p less than .05). Despite the same serum potassium values, the net potassium balance for 48 hrs was positive in the treatment group (plus 72 plus minus 32 mmol) and negative in the control group (minus 74 plus minus 95 mmol, p less than .05). There were no complications associated with the magnesium sulfate administration.

Conclusions: Magnesium sulfate administered according to the above regimen safely and significantly increases the circulating magnesium concentration. Despite greater urine magnesium losses in the treatment group, this group exhibited significantly better magnesium retention. In addition, within 30 hrs of entry into the study, the treatment group exhibited a net positive and statistically significant (p less than .05) improvement in potassium balance compared with the control group.

(Crit Care Med 1996; 24:38-45)

(C) Williams & Wilkins 1996. All Rights Reserved.