Potassium repletion fails to interfere with reduction of serum lithium by sodium polystyrene sulfonate in mice.

OBJECTIVES: Previous studies have shown that oral sodium polystyrene sulfonate (SPS) lowers serum lithium concentrations after acute and chronic toxic lithium exposures. Because hypokalemia may represent a deterrent to the clinical use of SPS for lithium intoxication, this study was designed to determine whether potassium (K+) repletion interferes with the effect of SPS on serum lithium. METHODS: 168 male, CD-1 mice were given lithium chloride (LiCl) (250 mg/kg) by gavage at time 0. Half of the mice were then given SPS (5 g/kg/dose) and half an equivalent volume of water by gavage at times 20 and 40 minutes. Half of each of these subgroups was then given potassium chloride (KCl) (3 mmol/kg) intraperitoneally and half an equivalent volume of normal saline. The animals were then sacrificed at one, two, four, and eight hours after lithium administration and the sera were analyzed for lithium and K+ by atomic absorption spectrophotometry. The groups were compared with analysis of variance. RESULTS: The SPS lowered both lithium and K+ concentrations (ps < or = 0.0001). The KCl treatment was associated with transiently increased K+ concentrations (p < 0.0001) and with mildly elevated lithium concentrations when compared with the results of the animals not treated with KCl (p = 0.0016). The KCl treatment-associated increase in lithium concentration occurred both in the animals treated with water and in those treated with SPS. CONCLUSIONS: Potassium repletion did not interfere with the ability of SPS to lower serum lithium concentration in animals experimentally poisoned with lithium.

Effect of delayed treatment with sodium polystyrene sulfonate on serum lithium concentrations in mice.

OBJECTIVES: To determine the efficacy of sodium polystyrene sulfonate (SPS) in lowering serum lithium (Li) concentrations. Specifically, to determine the effects of both different doses of SPS and different times to treatment with SPS on serum Li levels. METHODS: The study was a controlled, single-dose murine trial of SPS on serum Li levels. Male CD-1 mice (n = 525) were given orogastric LiCl and then divided into three main treatment groups: group SPS received a single orogastric administration of SPS in a dose of 5 gm/kg body weight at either 0, 15, 30, 45, or 90 minutes after LiCl; group half-SPS received a single orogastric administration of SPS in a dose of 2.5 gm/kg body weight at times equivalent to those of group SPS; and the control group received orogastric deionized water in a volume equivalent to that of group SPS at 0, 15, 30, 45, or 90 minutes after LiCl. Subgroups of seven to ten mice in each of the four treatment groups were sacrificed at one, two, four, and eight hours after administration of LiCl, and their blood was analyzed for Li concentration. RESULTS: 1) Single doses of SPS significantly lowered serum Li concentrations; 2) this effect was dose-related; 3) the delays in administration of SPS used in this study did not significantly reduce its ability to lower serum Li concentrations; and 4) even when administered after peak serum Li concentrations had been achieved, a single dose of SPS was effective in lowering serum Li levels. CONCLUSIONS: SPS may be efficacious in the treatment for Li toxicity under certain circumstances, even when there is delay to treatment. Additional study is warranted to further characterize the ability of SPS to alter Li kinetics.

Enhancement of lithium elimination by multiple-dose sodium polystyrene sulfonate.

OBJECTIVE: To determine whether multiple doses of sodium polystyrene sulfonate (SPS) enhance the elimination of IV-administered lithium (Li). METHODS: The study was a placebo-controlled, investigator-unblinded, murine trial of multiple doses of SPS on serum Li concentrations. Seventy-five male CD-1 mice were given IV pretreatment with LiCl (125 mg/ kg) followed by gavage treatments with SPS (5 g/kg/dose) 20, 40, 90, 150, and 210 minutes after LiCl (experimental group) or deionized water at equivalent times (control group). Subgroups of each treatment group were sacrificed at 1, 2, 4, and 6 hours after LiCl administration and blood was collected for Li analysis. RESULTS: Statistical analyses indicated that the SPS group had lower serum Li concentrations overall than did the control animals. This difference was apparent at the 2-, 4-, and 6-hour time points. CONCLUSION: In this murine model, repetitive doses of orogastric SPS enhanced the elimination of parenterally administered Li.

Sodium polystyrene sulfonate treatment for lithium toxicity: effects on serum potassium concentrations.

OBJECTIVE: To examine the effects of sodium polystyrene sulfonate (SPS) on serum potassium (K) concentrations in mice pretreated with parenteral lithium (Li). METHODS: A placebo-controlled murine model trial of SPS therapy following IV Li was performed. Sixty male CD-1 mice weighing 18-22 g were administered either IV LiCl (125 mg/kg) or a control solution (normal saline). Half of the mice in each of these groups were then given orogastric water 20, 40, 90, 150, and 210 minutes after LiCl or normal saline; the other half received SPS (5 g/kg/dose) at equivalent times. Subgroups of each of these four groups were sacrificed at one, two, and six hours after pretreatment and the serum was analyzed for K concentration. Serum K concentrations for the various groups were compared with analysis of variance and Newman-Keuls tests for the comparison of multiple means. RESULTS: A statistically significant reduction of serum K concentrations occurred in the animals that received SPS treatment following either IV saline or LiCl solutions. The degree of K reduction that resulted from the combination of LiCl and SPS treatment (35% reduction at six hours, compared with the placebo-treated controls) was larger than that which resulted from either IV Li with oral water (15% reduction) or IV saline with oral SPS (20% reduction). CONCLUSIONS: These findings suggest that development of hypokalemia may represent a potential limitation in the use of SPS in the treatment for Li toxicity.

Use of sodium polystyrene sulfonate for reduction of plasma lithium concentrations after chronic lithium dosing in mice.

OBJECTIVES: Previous studies have shown that oral sodium polystyrene sulfonate lowers plasma lithium concentrations after acutely administered oral doses of lithium chloride. However, a significant proportion of lithium overdose cases resulting in morbidity and mortality are those in which exposure to lithium is chronic. This study was designed to determine whether multiple oral doses of sodium polystyrene sulfonate are effective in reducing plasma lithium concentrations after chronic dosing. DESIGN: Placebo-controlled animal study. INTERVENTIONS: One hundred thirty mice were given 75 mM lithium chloride in their drinking water for a period of 14 days. At the end of that period, half of the animals were given orogastric sodium polystyrene sulfonate at 5 g/kg/dose 0, 60, 120, 180, and 360 minutes after the cessation of lithium chloride; the remaining half received orogastric water at equivalent times. Subgroups of each group were sacrificed at 90, 150, 330, 480, 1440, and 2880 minutes after lithium chloride cessation and plasma analyzed for lithium content. Lithium concentrations were compared by analysis of variance and single degree of freedom contrasts. Significance was set at an alpha level of 0.05. RESULTS: Lithium concentration was lower overall in the animals treated with sodium polystyrene sulfonate (p < .0001) and specifically at 150, 330, and 480 minutes after lithium chloride cessation (p < .05). CONCLUSIONS: Repetitive oral doses of sodium polystyrene sulfonate effectively lowered plasma lithium concentrations. Further study may ultimately define a role for the use of sodium polystyrene sulfonate in the treatment of patients with chronic lithium toxicity.

Administration of activated charcoal or sodium polystyrene sulfonate (Kayexalate) as gastric decontamination for lithium intoxication: an animal model.

To determine whether sodium polystyrene sulfonate (SPS; Kayexalate) is effective in decreasing the absorption of lithium (Li) and to test the assumption that Li is poorly adsorbed by activated charcoal, 130 mice were administered an orogastric dose of LiCl (250 mg/kg) followed immediately by orogastric SPS (10 g/kg, SPS Group), activated charcoal (6.7 g/kg, AC Group), or water in an equivalent volume (Control Group). Subgroups of each of the 3 groups were sacrificed at 1, 2, 4 and 8 hr after treatment and serum analyzed for Li concentration. Statistical analyses revealed no overall difference between the AC Group and the Control Group. However, the SPS Group differed from both the Control and the AC Group at each time interval, with Li concentrations significantly lower in the SPS Group. These results demonstrate that: 1) SPS, in this study, effectively reduced serum Li concentrations in an in vivo model, and 2) activated charcoal did not.

Multiple-dose sodium polystyrene sulfonate in lithium intoxication: an animal model.

Previous work in our laboratory has demonstrated that sodium polystyrene sulfonate (SPS) significantly lowered serum lithium (Li) concentrations when administered in a single oral dose after an oral dose of lithium in a mouse model. The present study was designed to determine whether: 1) repetitive doses of SPS are effective in lowering serum lithium concentrations, 2) the effect of SPS on lithium concentration is dose related and 3) SPS enhances the elimination of lithium. Mice (N = 144) were given orogastric LiCl (250 mg/kg) and then divided into 4 groups: Controls received water 0, 30, 90, 180, and 360 min. after LiCl; the Full-Dose SPS Group received SPS (5 g/kg/dose) at equivalent times; the Half-Dose SPS Group received SPS (2.5 g/kg/dose) at the same times; and the Elimination Group received water at 0 and 30 min. after LiCl and SPS at 90, 180 and 360 min. after LiCl. Subgroups of each group were sacrificed at 1, 2, 4 and 8 hr post-treatment and serum analyzed for lithium concentrations. Statistical analyses revealed that, when compared to Controls: 1) SPS significantly lowered serum lithium concentrations; 2) this effect was dose-related; 3) repetitive dosing of SPS appears to enhance the elimination of lithium.