MAGNESIUM REPLETION AND ITS EFFECT ON POTASSIUM HOMEOSTASIS IN CRITICALLY ILL ADULTS - RESULTS OF A DOUBLE-BLIND, RANDOMIZED, CONTROLLED TRIAL

Objectives: The aims of this study were to evaluate the safety and eff icacy 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. Sett ing: A surgical intensive care unit (ICU). Patients: A total of 32 adu lt surgical ICU patients were admit ted to the study on the basis of d ocumented hypokalemia (potassium of <3.5 mmol/L) within the 24-hr peri od before entering the study. Patients were randomized to receive eith er placebo (n = 15) or magnesium sulfate (n = 17). One patient from ea ch group was excluded from the study due to failure to complete the fu ll series of doses. Interventions: Patients received a ''test dose'' o f either magnesium sulfate (2 g, 8 mmol) or placebo (5% dextrose in wa ter) infused over 30 mins every 6 hrs for eight doses. The next schedu led test dose was held if hypermagnesemia (magnesium of >2.8 mg/dL [>1 .15 mmol/L]) was documented at any time during the study. Routine repl acements of potassium and magnesium continued during the duration of t he study, when clinically indicated, for serum potassium concentration s of 3.5 mmol/L or serum magnesium concentrations of <1.8 mg/dL (<0.74 mmol/L). Measurements and Main Results: Age, weight, and Acute Physio logy and Chronic Health Evaluation II scores were recorded on entry in to the study. Just before administration of each test dose, blood was drawn for magnesium and potassium, bicarbonate, pH, and glucose determ inations, and an aliquot of the preceding 6 hrs urine collection was s ent for magnesium and potassium determinations. Serum calcium, phospha te, urea nitrogen, and creatinine concentrations were measured daily. The amounts of magnesium and potassium administered via parenteral nut rition, tube feeding, and replacement infusions were calculated for ea ch 6-hr interval. The amounts of magnesium and potassium excreted in t he urine were similarly assessed. The groups showed no differences wit h regard to age, weight, Acute Physiology and Chronic Health Evaluatio n II scores, or initial serum magnesium concentration. Initial potassi um, bicarbonate, pH, calcium, phosphate, glucose, blood urea nitrogen, and creatinine values were not different between groups. Patients rec eiving magnesium sulfate showed a statistically significant increase i n serum magnesium concentration at 6 hrs when compared with placebo, a s well as with itself at time 0 (p < .0001), a difference maintained t hroughout the study. Compared with the placebo group, the total amount of elemental magnesium administered was significantly greater in the treatment group (1603 +/- 124 vs. 752 +/- 215 mg [65.7 +/- 5.8 vs. 30. 8 +/- 8.8 mmol], p < .0001), as was urine magnesium excretion (1000 +/ - 156 vs. 541 +/- 68 mg [41.0 +/- 6.4 vs. 22.2 +/- 2.8 mmol] p < .0001 ). However, the net magnesium balance (total magnesium in - total urin e magnesium) was significantly more positive in the treatment group (6 12 +/- 180 vs. 216 +/- 217 mg [25.1 +/- 7.4 vs. 8.9 +/- 8.9 mmol], p < .005). The treatment and control groups had the same serum potassium concentrations and did not receive different amounts of potassium (245 +/- 39 vs. 344 +/- 45 mmol, respectively, p = .06), although the trea tment group required less potassium replacement/6 hrs by 30 hrs compar ed with itself at time 0 (p < .05). Despite the same serum potassium v alues, the net potassium balance for 48 hrs was positive in the treatm ent group (+72 +/- 32 mmol) and negative in the control group (-74 +/- 95 mmol, p < .05). There were no complications associated with the ma gnesium sulfate administration. Conclusions: Magnesium sulfate adminis tered according to the above regimen safely and significantly increase s the circulating magnesium concentration. Despite greater urine magne sium 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 statistica lly significant (p < .05) improvement in potassium balance compared wi th the control group.