Magnesium Replacement Research Articles

Diabetic coma. Management of diabetic ketoacidosis and nonketotic hyperosmolar coma

This review describes the current guidelines of German diabetes association for the management of diabetic coma, both of diabetic ketoacidosis and hyperosmolal coma. The outline focuses on emergency treatment and the management on the intensive care unit, in particular, volume and insulin therapy, and potassium replacement. The delineation of the concept of low insulin therapy is emphasized to avoid the incidence of disequilibrium syndrome. Also, the indications for bicarbonate therapy in diabetic ketoacidosis are critically discussed, as well as phosphate and magnesium replacement. With today's therapeutic possibilities the therapeutic goal, i.e. a low mortality, may be achieved, dependent on the underlying illness.

Independent Effects of Nitrogen Substitution for Oxygen and Yttrium Substitution for Magnesium on the Properties of Mg‐Y‐Si‐Al‐O‐N Glasses

Glasses of composition (in equivalent percent) (28 −x)Mg:xY:56Si:16Al:(100 −y)O:yN, with x= 0, 14, or 28 for y= 0 and 15 and with x= 0, 7, 14, 21, or 28 for y= 10, were prepared by melting and casting. For glasses where the nitrogen content was varied for a constant cationic ratio, the glass molar volume (MV), compactness (C), Young's modulus (E), glass‐transition temperature (Tg), and dilatometric‐softening temperature (Tds) varied linearly as the nitrogen content increased, with MV decreasing and the other properties increasing. From the incremental changes in these properties with nitrogen content, for glasses with x= 0, 14, and 28, good linear fits (R2 > 0.99) were obtained, and best‐fit slopes are reported here. The property changes and their linearity were consistent with the increased cross‐linking of the glass network by tricoordinated nitrogen. The replacement of magnesium by yttrium led to a nonlinear decrease in glass compactness and to nonlinear increases in MV, Tg, and Tds. However, linear correlations were found for MV and ionic volume and for Tg, Tds, and the coordination of (Si,Al)(O,N) tetrahedra of the glass structural units to the modifier cations not involved in charge compensating aluminum ions in fourfold coordination. The replacement of magnesium by yttrium had little effect on Young's modulus, and this result was related to similar changes in the compactness, C. The present results showed that the effects of substituting nitrogen for oxygen and yttrium for magnesium are independent and additive; thus, no synergistic effects of anion and cation substitutions were observed.

THE 2002 MOYER AWARD

Abstract Severe burn injury results in profound metabolic derangements. Recently, we have shown that vitamin D metabolism is disturbed after burn injury. Vitamin D is essential for calcium and phosphorus homeostasis and skeletal bone integrity. The role of vitamin D on magnesium homeostasis is not well understood. The purpose of this study was to assess the effects of vitamin D deficiency on serum electrolytes. Forty-one pediatric burn patients with a mean (± SEM) total body surface area burn of 53.1 ± 2.9% and full-thickness injury of 44.2 ± 4.1% were studied from July 1996 to December 2000. The mean age of the patients was 6.5 ± 0.8 years. Patients were studied for 6 weeks after admission to the hospital. Blood samples were obtained weekly for serum 25-hydroxycholecalciferol (25D), 1,25-dihydroxycholecalciferol (1,25D), and daily for calcium, magnesium, and phosphorus. Total intravenous (IV) replacement of calcium, magnesium, and phosphorus was also quantitated retrospectively. Bivariate and multivariate correlational analysis was used for statistical comparison. For the study duration, multivariate analysis demonstrated a positive correlation between 25D and serum calcium (r = .47, P < .05) and 1,25D and calcium (r = .27, P < .05). Overall, calcium had a positive correlation with phosphorus and a negative correlation with IV calcium replacement (ie, patients with lower calcium received more IV replacement). During the initial week of hospitalization (week 0), decreased 25D (mean 11.6 ng/ml; normal range 15–57 ng/ml) and 1,25D (mean 13.9 pg/ml; normal range 15–75 pg/ml) did not correlate with any other measured variable. In week 1, 1,25D (mean 15.2 ng/ml) had a positive correlation (r = .410, P < .05) with calcium (mean 7.70 mg/dl). Hypovitaminosis D observed in burn injury correlates with serum calcium and phosphorus abnormalities. Early after injury (<1 week) there was no observed correlation between vitamin D and other variables possibly because of the effects of burn shock. After 1 week, vitamin D appears to significantly effect phosphorus homeostasis. The relationship between vitamin D and magnesium is not well established. These results may indicate a role for vitamin D replacement therapy during the initial phase of burn resuscitation.

Denitrification of natural water on supported Pd/Cu catalysts

The influence of the support on the catalytic hydrogenation of nitrates in liquid phase was investigated. Pd/Cu supported on hydrotalcite and Pd/Cu supported on alumina catalysts were tested for this reaction and its activity and selectivity were compared. It has been observed a higher activity and a lower production of ammonium when the metals are supported on hydrotalcite than when they are supported on alumina. When rehydrated after calcination hydrotalcite recovers its layered structure. Nitrates can be located in the interlayer space diminishing the problems associated to mass transfer limitations and increasing the activity of the material. In addition, copper can be incorporated in the hydrotalcite structure by an isomorphical replacement of magnesium, obtaining thus a high dispersion of the copper centres, that is reflected in a higher activity if compared with copper impregnated samples. A XPS study was made in order to characterise the metals supported on the hydrotalcite.

Metabolic Effects of Vitamin D on Serum Calcium, Magnesium and Phosphorus in Pediatric Burn Patients

Severe burn injury results in profound metabolic derangements. Recently, we have shown that vitamin D metabolism is disturbed after burn injury. Vitamin D is essential for calcium and phosphorus homeostasis and skeletal bone integrity. The role of vitamin D on magnesium homeostasis is not well understood. The purpose of this study was to assess the effects of vitamin D deficiency on serum electrolytes. Forty-one pediatric burn patients with a mean (± SEM) total body surface area burn of 53.1 ± 2.9% and full-thickness injury of 44.2 ± 4.1% were studied from July 1996 to December 2000. The mean age of the patients was 6.5 ± 0.8 years. Patients were studied for 6 weeks after admission to the hospital. Blood samples were obtained weekly for serum 25-hydroxycholecalciferol (25D), 1,25-dihydroxycholecalciferol (1,25D), and daily for calcium, magnesium, and phosphorus. Total intravenous (IV) replacement of calcium, magnesium, and phosphorus was also quantitated retrospectively. Bivariate and multivariate correlational analysis was used for statistical comparison. For the study duration, multivariate analysis demonstrated a positive correlation between 25D and serum calcium (r = .47, P <.05 ) and 1,25D and calcium (r =.27, P <.05). Overall, calcium had a positive correlation with phosphorus and a negative correlation with IV calcium replacement (ie, patients with lower calcium received more IV replacement). During the initial week of hospitalization (week 0), decreased 25D (mean 11.6 ng/ml; normal range 15-57 ng/ml) and 1,25D (mean 13.9 pg/ml; normal range 15-75 pg/ml) did not correlate with any other measured variable. In week 1, 1,25D (mean 15.2 ng/ml) had a positive correlation (r =.410, P <.05) with calcium (mean 7.70 mg/dl). Hypovitaminosis D observed in burn injury correlates with serum calcium and phosphorus abnormalities. Early after injury (< 1 week) there was no observed correlation between vitamin D and other variables possibly because of the effects of burn shock. After 1 week, vitamin D appears to significantly effect phosphorus homeostasis. The relationship between vitamin D and magnesium is not well established. These results may indicate a role for vitamin D replacement therapy during the initial phase of burn resuscitation.

The 2002 Moyer Award. Metabolic effects of vitamin D on serum calcium, magnesium, and phosphorus in pediatric burn patients.

Severe burn injury results in profound metabolic derangements. Recently, we have shown that vitamin D metabolism is disturbed after burn injury. Vitamin D is essential for calcium and phosphorus homeostasis and skeletal bone integrity. The role of vitamin D on magnesium homeostasis is not well understood. The purpose of this study was to assess the effects of vitamin D deficiency on serum electrolytes. Forty-one pediatric burn patients with a mean (+/- SEM) total body surface area burn of 53.1 +/- 2.9% and full-thickness injury of 44.2 +/- 4.1% were studied from July 1996 to December 2000. The mean age of the patients was 6.5 +/- 0.8 years. Patients were studied for 6 weeks after admission to the hospital. Blood samples were obtained weekly for serum 25-hydroxycholecalciferol (25D), 1,25-dihydroxycholecalciferol (1,25D), and daily for calcium, magnesium, and phosphorus. Total intravenous (IV) replacement of calcium, magnesium, and phosphorus was also quantitated retrospectively. Bivariate and multivariate correlational analysis was used for statistical comparison. For the study duration, multivariate analysis demonstrated a positive correlation between 25D and serum calcium (r =.47, P <.05) and 1,25D and calcium (r =.27, P <.05). Overall, calcium had a positive correlation with phosphorus and a negative correlation with IV calcium replacement (ie, patients with lower calcium received more IV replacement). During the initial week of hospitalization (week 0), decreased 25D (mean 11.6 ng/ml; normal range 15-57 ng/ml) and 1,25D (mean 13.9 pg/ml; normal range 15-75 pg/ml) did not correlate with any other measured variable. In week 1, 1,25D (mean 15.2 ng/ml) had a positive correlation (r =.410, P <.05) with calcium (mean 7.70 mg/dl). Hypovitaminosis D observed in burn injury correlates with serum calcium and phosphorus abnormalities. Early after injury (<1 week) there was no observed correlation between vitamin D and other variables possibly because of the effects of burn shock. After 1 week, vitamin D appears to significantly effect phosphorus homeostasis. The relationship between vitamin D and magnesium is not well established. These results may indicate a role for vitamin D replacement therapy during the initial phase of burn resuscitation.

Acute spinal cord injury, part II: contemporary pharmacotherapy.

Spinal cord injury (SCI) remains a common and devastating problem of modern society. Through an understanding of underlying pathophysiologic mechanisms involved in the evolution of SCI, treatments aimed at ameliorating neural damage may be developed. The possible pharmacologic treatments for acute spinal cord injury are herein reviewed. Myriad treatment modalities, including corticosteroids, 21-aminosteroids, opioid receptor antagonists, gangliosides, thyrotropin-releasing hormone (TRH) and TRH analogs, antioxidants and free radical scavengers, calcium channel blockers, magnesium replacement therapy, sodium channel blockers, N -methyl-D-aspartate receptor antagonists, alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid-kainate receptor antagonists, modulators of arachadonic acid metabolism, neurotrophic growth factors, serotonin antagonists, antibodies against inhibitors of axonal regeneration, potassium channel blockers (4-aminopyridine), paclitaxel, clenbuterol, progesterone, gabexate mesylate, activated protein C, caspase inhibitors, tacrolimus, antibodies against adhesion molecules, and other immunomodulatory therapy have been studied to date. Although most of these agents have shown promise, only one agent, methylprednisolone, has been shown to provide benefit in large clinical trials. Given these data, many individuals consider methylprednisolone to be the standard of care for the treatment of acute SCI. However, this has not been established definitively, and questions pertaining to methodology have emerged regarding the National Acute Spinal Cord Injury Study trials that provided these conclusions. Additionally, the clinical significance (in contrast to statistical significance) of recovery after methylprednisolone treatment is unclear and must be considered in light of the potential adverse effects of such treatment. This first decade of the new millennium, now touted as the Decade of the Spine, will hopefully witness the emergence of universal and efficacious pharmacologic therapy and ultimately a cure for SCI.

Hypomagnesemia in short bowel syndrome patients

Magnesium support to small bowel resection patients. Incidence and treatment of hypomagnesemia in patients with extensive small bowel resection. Retrospective study. Metabolic Unit of the University Hospital Medical School of Ribeirão Preto, University of São Paulo, Brazil. Fifteen patients with extensive small bowel resection who developed short bowel syndrome. Serum magnesium control of patients with bowel resection. Replacement of magnesium when low values were found. Initial serum magnesium values were obtained 21 to 180 days after surgery. Hypomagnesemia [serum magnesium below 1.5 mEq/l (SD 0.43)] was detected in 40% of the patients [1,19 mEq/l (SD 0.22)]. During the follow-up period, 66% of the patients presented at least two values below reference (1.50 mEq/l). 40% increased their serum values after magnesium therapy. Metabolic control of serum magnesium should be followed up after extensive small bowel resection. Hypomagnesemia may be found and should be controlled.

Interaction of cyclosporine and FK506 with diuretics in transplant patients

The calcineurin inhibitors cyclosporine and FK506 are widely used for immunosuppression in solid organ transplantation. One of the side effects of these agents is renal magnesium wasting. The site of action and molecular mechanism of this effect are not known. We hypothesized that agents such as diuretics that cause renal magnesium wasting through a similar action would not have an additive effect on magnesium deficiency with calcineurin inhibitors. The records of 50 heart transplant patients on calcineurin inhibitors were reviewed to determine levels of serum magnesium and required replacement dose of magnesium, diuretic usage, and other laboratory values. Loop diuretics did not change either the magnesium level or magnesium replacement requirements in patients on calcineurin inhibitors. In contrast, the thiazide diuretic resulted in an increase in serum magnesium and a decrease in magnesium replacement. Results were similar when the cyclosporine or FK506 groups were evaluated alone. Patients taking FK506 had lower serum magnesium values and higher requirements for magnesium replacement compared with patients taking cyclosporine. We conclude that calcineurin inhibitors and loop diuretics have a similar site of action.

Enhanced tumor necrosis factor-α production following endotoxin challenge in rats is an early event during magnesium deficiency

Magnesium (Mg) plays an essential role in fundamental cellular reactions and the importance of the immuno-inflammatory processes in the pathology of Mg deficiency has been recently reconsidered. The purpose of the present study was to assess the effect of different stages of Mg deficiency on endotoxin response and tumor necrosis factor-α (TNFα) production. Weaning male Wistar rats were pair fed either a Mg-deficient or a control diet. At day 7, lipopolysaccharide (LPS) induced no lethal effects in control rats but resulted in 70% mortality in Mg-deficient rats within 3 h. The vulnerability of Mg-deficient rats to LPS was associated with higher TNFα plasma values. Mg-deficient animals that received magnesium supplementation before endotoxin challenge had significantly increased survival. At day 2, control and Mg-deficient rats were also subjected to endotoxin challenge with or without magnesium pre-treatment. A significant increase in TNFα plasma level was observed in Mg-deficient rats compared to rats fed the control diet. Mg-deficient rats that received magnesium replacement therapy before endotoxin challenge had significantly lower TNFα plasma values than those receiving saline before endotoxin. Thus, the results of this experiment suggest that the activated or primed state of immune cells is an early event occurring in Mg deficiency.

HYPOMAGNESAEMIA IN POSTOPERATIVE PATIENTS: AN IMPORTANT CONTRIBUTING FACTOR IN POSTOPERATIVE MORTALITY

SUMMARYMagnesium is the second most abundant intracellular cation and the fourth most abundant cation in the body. Clinical manifestations of hypomagnesaemia include neuromuscular, neurological, psychiatric and cardiac arrhythmias including torsade de pointes resulting in sudden death. Incidence of hypomagnesaemia in hospitalised patients is common and there is a lack of clinical awareness. Clinicians should become familiar with the common conditions and therapeutics that are risk factors for underlying hypomagnesaemia and become familiar with magnesium replacement regimens. Two patients who suffered fatal complications in whom hypomagnesaemia was an important contributing factor are presented. Hypokalaemia and hypocalcaemia are common in severe magnesium deficiency and require concurrent monitoring and correcting.

Serum magnesium levels and urinary magnesium excretion in patients with chronic constipation

Numerous etiologies for constipation are well recognized including abnormalities of serum electrolytes, most notably potassium and calcium. The dynamics of magnesium balance in patients with constipation is poorly understood. The index patient for this study was a 49 year old woman admitted to the hospital for abdominal pain associated with severe, life-long constipation. No other medical problems were identified. Her serum magnesium on admission was 1.6 mg/dl (nl 1.8-2.4). Serum bicarbonate was 20 mEq/1 suggesting renal tubular acidosis, possibly accounting for her hypomagnesemia through renal magnesium wasting. Urine magnesium was 37.4 mg/24hr (nl 12-293). Constipation improved with oral magnesium replacement. Five other patients with life-long constipation have also been found to have low serum magnesium (1.6 _+ 0.5 mg/dl; n=6, mean-SD). Only one patient had an appropriate urinary magnesium (less than 12 mg/24hrs) with the mean urinary magnesium of all six patients being 61.3 +-43.3 mg/24hr (range 10 to 102.2). All patients had early improvement in constipation symptoms with normalization of serum magnesium levels; however, long-term follow-up is not available at this time. In order to determine the prevalence of hypomagnesemia in the patient population with idiopathic constipation, we performed serum magnesium measurements on 25 consecutive patients with moderate to severe constipation (fewer than two spontaneous bowel movements a week). The mean magnesium level was 1.85+0.16 mg/dl. Seven patients were below the lower limit of normal in our laboratory (1.8). Hypomagnesemia associated with renal magnesium wasting may adversely influence colonic motility in a proportion of patients with life-long constipation.

The Hydration and Dissolution of Periclase

The dissolution of powdered periclase, MgO, in near neutral to acidic solutions, proceeds via a brucite, Mg(OH)2, intermediate. The hydration reaction is apparent from the similarity of the dissolution rates (Vermilyea, 1969) and X-ray diffraction of the reacting powder. There is evidence from both natural samples (Gorshkov et al. , 1992) and calculations (Refson et al., 1995) that a topotactic relationship exists between the (111) planes of periclase and the (0001) planes of brucite. Calculations indicate that the dissociation of water on the (001) surface is endothermic. Chemisorption on surfaces comprising atoms of lower coordination is more favourable, with the hydroxylated (111) surface being of lowest energy (Refson et al., 1995; de Leeuw et al., 1995). A proposed reaction mechanism involves the replacement of magnesium by hydrogen along (111) periclase planes. This was studied for the periclase (001) surface. Elastic recoil detection analysis (ERDA) results have been reported which suggested the formation of a 1000 ,~ layer with composition Mg(OH)2 for a sample reacted at pH 2 for 2 hours (Wogelius et al., 1995). In this paper we present ERDA and SIMS results which contradict this finding.

Macrocyclic Cu(II)(2), Cu(II)(4), Ni(II)(3), and Ni(II)(4) Complexes: Magnetic Properties of Tetranuclear Systems.

A binuclear tetraprotonated macrocyclic complex [Mg(2)(L(2)-H(4))(NO(3))(2)](NO(3))(2).6H(2)O (1) has been obtained by template condensation of 4-methyl-2,6-diformylphenol and 1,2-diaminoethane in the presence of magnesium acetate and nitrate. Complex 1 on reduction with NaBH(4), followed by the removal of magnesium, yields the 36-membered octaaminotetraphenol macrocyclic ligand H(4)L(1). The replacement of magnesium in 1 with copper(II) leads to the formation of the binuclear complex [Cu(2)L(3)(ClO(4))(2)] (2) derived from the [2+2] cyclization product of 4-methyl-2,6-diformylphenol and 1,2-diaminoethane. From H(4)L(1) a series of tetranuclear nickel(II) complexes 5-8 with the core cation [Ni(4)L(1)(&mgr;(2)-X)(2)(&mgr;(2)-H(2)O)(2)](2+) (X = NCS, N(3), OAc, or Cl) have been synthesized and characterized. The trinuclear complex [Ni(3)L(1)(acac)(2)(H(2)O)(2).2H(2)O (9), obtained by reacting nickel(II) acetylacetonate with H(4)L(1), on treatment with nickel(II) perchlorate produces the tetranuclear compound [Ni(4)L(1)(acac)(2)(H(2)O)(4)](ClO(4))(2) (10). Variable-temperature (4-300 K) magnetic susceptibility measurements have been carried out for the tetracopper(II) complex [Cu(4)L(1)(H(2)O)(4)](ClO(4))(4) (3) and the tetranickel(II) complexes [Ni(4)L(1)(&mgr;(3)-OH)(&mgr;(2)-H(2)O)(2)(ClO(4))](ClO(4))(2).2CH(3)COCH(3).H(2)O (4), [Ni(4)L(1)(&mgr;(2)-NCS)(2)(&mgr;(2)-H(2)O)(2)](ClO(4))(2).2CH(3)CN (5), [Ni(4)L(1)(&mgr;(2)-N(3))(2)(&mgr;(2)-H(2)O)(2)](ClO(4))(2).2CH(3)OH (6), [Ni(4)L(1)(&mgr;(2)-OAc)(2)(&mgr;(2)-H(2)O)(2)](ClO(4))(2).2H(2)O (7), and [Ni(4)L(1)(&mgr;(2)-Cl)(2)(&mgr;(2)-H(2)O)(2)]Cl(2).4H(2)O (8). The X-ray structure of 5 has been determined. The complex (C(50)H(70)N(12)O(14)Cl(2)S(2)Ni(4)) crystallizes in the triclinic space group P&onemacr; with a = 11.794(6) Å, b = 12.523(4) Å, c = 12.794(5) Å, alpha = 117.28(5) degrees, beta = 96.38(4) degrees, gamma = 109.65(3) degrees, and Z = 1. In the asymmetric unit each of the nickel(II) centers with distorted octahedral geometry is triply-bridged by a phenoxide group, a water molecule, and a N-bonded thiocyanate and these metal centers are further bridged to their symmetry-related counterparts by another phenoxide group. The experimental susceptibility data have been analyzed using appropriate Heisenberg spin coupling models (H = -2J(ij)()S(i)().S(j)()) and the best-fit spin exchange parameters obtained are as follows: J = -288(3) cm(-)(1) (3); J(1) = -8.1(2) cm(-)(1), J(2) = -10.2(2) cm(-)(1) (4); J(1) = -34.5(1.0) cm(-)(1), J(2) = -9.5(2.0) cm(-)(1) (5); J(1) = -34(1) cm(-)(1), J(2) = 11(2) cm(-)(1) (6); J(1) = -30(1) cm(-)(1), J(2) = -7.0(1.5) cm(-)(1) (7); J(1) = -32(1) cm(-)(1), J(2) = -4(1) cm(-)(1) (8).

Effects of external calcium on zinc modulation of AMPA receptors

The effects of calcium on zinc modulation of current responses from two similar homomeric glutamate receptors, GluR1 and GluR3, was examined using the Xenopus oocyte expression system. Previous experiments carried out using normal (calcium-containing) physiological solution showed that kainate-evoked current responses from GluR3, but not GluR1, were potentiated by low μM concentrations of zinc. Furthermore this potentiation was observed only over a narrow range of zinc concentrations. In contrast, the present experimens demonstrated that in calcium-free solution (magnesium replacement) zinc can potentiate both GluR3, as expected, but also GluR1. In addition, the potentiation occurs over a large range of zinc concentrations (> log units). Re-supply of calcium to the solution interferes with zinc potentiation in a concentration-dependent manner. When supernormal concentrations of calcium are present, zinc greatly inhibits currents at zinc concentrations that would cause potentiation in the absence of calcium, and that would cause smaller inhibition in normal solution. Because zinc is co-released along with neurotransmitter at many glutamatergic synapses in vertebrate brains, and synaptic calcium levels are subject to variable control, calcium regulation of zinc sensitivity may be physiologicall relevant.

Hypomagnesemia in postoperative spine fusion patients.

This was a retrospective review of 49 consecutive patient charts and a prospective study of 44 consecutive patients who underwent spinal fusion. To determine the incidence and clinical significance of hypomagnesemia after spinal fusion. Hypomagnesemia may be seen in 61% of patients in postoperative intensive care and may be associated with increased mortality. However, symptomatic hypomagnesemia is rare. A retrospective review of the charts of 49 consecutive patients who underwent spine fusion was completed to determine postoperative magnesium levels. Twenty-seven patients with postoperative hypomagnesemia received routine magnesium replacement regardless of symptoms. Forty-four patients who underwent spine fusion were studied prospectively for postoperative hypomagnesemia. Prospectively studied observational patients who developed hypomagnesemia were treated only when clinical signs or symptoms of magnesium deficiency occurred. Postoperative hypomagnesemia occurred in 28 of 49 retrospectively studied patients who underwent spine fusion (57%) and 38 of 44 prospectively studied patients who underwent spine fusion (86%). Symptoms associated with hypomagnesemia developed in three of 44 prospectively studied and two of 49 retrospectively studied patients who underwent spine fusion (7% and 4%, respectively). The combined incidence for symptomatic hypomagnesemia was five of 93 patients. (5.4%). The majority of patients from the prospective study with postoperative hypomagnesemia were asymptomatic, and their magnesium levels returned to normal within 4 days, with or without treatment. This study confirmed a high incidence of hypomagnesemia in patients who underwent spine fusion, although only 5.4% developed clinical signs or symptoms of magnesium deficiency. The cause of hypomagnesemia remains speculative.

Magnesium repletion and its effect on potassium homeostasis in critically ill adults

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. A prospective, double-blind, randomized, placebo-controlled trial. A surgical intensive care unit (ICU). A total of 32 adult surgical ICU patients were admitted to the study on the basis of documented hypokalemia (potassium of < 3.5 mmol/L) within the 24-hr period before entering the study. Patients were randomized to receive either placebo (n = 15) or magnesium sulfate (n = 17). One patient from each group was excluded from the study due to failure to complete the full series of doses. 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 schedule 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 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 < 1.8 mg/dL (< 0.74 mmol/L). 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 < .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 +/- 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 urine magnesium) was significantly more positive in the treatment group (612 +/- 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 treatment group required less potassium replacement/6 hrs by 30 hrs compared with itself at time 0 (p < .05). Despite the same serum potassium values, the net potassium balance for 48 hrs was positive in the treatment group (+ 72 +/- 32 mmol) and negative in the control group (-74 +/- 95 mmol, p < .05). There were no complications associated with the magnesium sulfate administration. Magnesium sulfate administered according to the above regimen safety and significantly increases the circulating magnesium concentration. Despite greater urine magnesium losses in the treatment group, this group exhibited significantly better magnesium retention.

A new microporous material: aluminated sepiolite

It was shown previously that the stability of the porous structure of sepiolite, a fibrous magnesio-silicate formed of staggered talc sheets, was improved by isomorphic replacement of silicon by aluminum in the tetrahedral sheet and some replacement of magnesium by aluminum in the octahedral sheet. Alumination was carried out using a caustic solution of sodium aluminate. Here, it is shown that further improvement can be achieved by aluminating with a caustic solution of potassium aluminate. As the number of substitutions in the tetrahedral layer increases, the cation-exchange capacity corresponding to the increase of the lattice negative charge reaches 0.55 mequiv./g. The microporosity is preserved up to 400°C while it collapsed at 150°C in the original sepiolite. The calcined ammonium-exchanged aluminated sepiolite contains mostly Lewis acid sites, contradictory to the expectation to observe some Brönsted sites. Because of the rather high cation-exchange capacity, cations with redox properties (such as Ag +) can be exchanged, leading to a bifunctional catalyst.

Pharmacologic Treatment of Congestive Heart Failure-Reply

In Reply. —We appreciate the comments of Dr Ahmad, Dr Anderson, and Dr Oosterbosch, expressed in an effort to improve the recommendations within the recent Agency for Health Care Policy and Research clinical practice guideline on heart failure1and in our recent publication inThe Journal. Ahmad raises the potential value of low-dose amiodarone. At this time, we do not believe that sufficient data exist to reach a consensus regarding the role of low-dose amiodarone for prolonging survival in heart failure. Currently available data are conflicting. A promising study, showing improved survival with amiodarone,2was published subsequent to the publication of the guideline. However, the study by Nicklas et al3referenced by Ahmad showed no clinical benefit. We believe that more data are needed to determine whether routine use of this agent is warranted. We concur with the comments of Anderson regarding the importance of magnesium replacement

Progressive magnesium deficiency increases mortality from endotoxin challenge: protective effects of acute magnesium replacement therapy.

To study the effects of endotoxin on magnesium homeostasis; to determine if progressive magnesium deficiency alters outcome from endotoxin challenge; and to evaluate the efficacy of magnesium therapy in reducing endotoxin-induced mortality. Prospective, placebo-controlled, randomized, multiexperiment studies. Research laboratory of a university hospital. Male Sprague Dawley rats (n = 299). Experiment 1 was designed to test if endotoxin alters magnesium homeostasis. Circulating total and ionized magnesium (estimated by ultrafilterable values) concentrations were determined in blood samples collected from animals after the randomized administration of placebo or 0.3, 3.0, or 30 mg/kg of endotoxin. A baseline blood sample was collected and then a second blood sample was obtained at 5, 15, 30, 60, 120, or 180 mins after endotoxin or placebo administration. In experiment 2, animals were randomized to receive magnesium-sufficient diets or magnesium-deficient diets for 6 wks. After 6 wks, the effects of the randomized administration of 3.0 mg/kg endotoxin or placebo were evaluated on mortality and analyte values (pH and blood gases, sodium, potassium, chloride, glucose, ionized calcium, hematocrit, total and ultrafilterable magnesium concentrations) in the three study groups (magnesium-sufficient, 3-wk magnesium-deficient, or 6-wk magnesium-deficient). In experiment 3, magnesium-deficient animals were randomized to receive 50 mmol/kg magnesium chloride or placebo, before or after the administration of 3.0 mg/kg of endotoxin. Baseline and 24-hr analyte determinations were performed and outcome was analyzed. Experiment 1: Significant increases (p < .05) in circulating total magnesium concentrations were found in animals that received 30 mg/kg of endotoxin, at 120 mins (0.79 +/- 0.10 vs. 0.60 +/- 0.05 mmol/L), and 180 mins (0.74 +/- 0.04 vs. 0.56 +/- 0.04 mmol/L) compared with baseline values. Similarly, significant increases (p < .05) in ionized magnesium concentrations were observed 120 and 180 mins after 3.0 and 30 mg/kg of endotoxin compared with baseline values. Experiment 2: Magnesium deficiency was strongly (p < .02) associated with increased mortality from endotoxin challenge. Endotoxin administration (3.0 mg/kg) was lethal in 10 (43%) of 23 magnesium-sufficient animals, 15 (65%) of 23 3-wk magnesium-deficient animals, and 20 (83%) of 24 6-wk magnesium-deficient animals. Experiment 3: In magnesium-deficient animals, rats treated with magnesium replacement therapy had significantly increased survival from endotoxin administration (15 [52%] of 29 vs. five [17%] of 29, p < .01) compared with placebo-treated animals. a) Endotoxin challenge causes significant increases in circulating total and ionized magnesium concentrations. b) Progressive magnesium deficiency is strongly associated with increased lethality, and magnesium replacement therapy provides significant protection from endotoxin challenge. c) These experimental results support the concept that cellular injury is probably associated with increases in circulating magnesium concentrations. Furthermore, these experimental findings suggest that magnesium deficiency predisposes to worse outcome from endotoxin challenge, and that replacement therapy in the setting of magnesium deficiency may be warranted, especially in critically ill subjects.