Effect of whole blood clotting time in rats with ionized hypocalcemia induced by rapid intravenous citrate infusion.

Although the toxic effects of citrate including hemodynamic and cardiovascular changes result from a decrease in ionized calcium levels in serum due to chelating action, these effects of citrate on blood coagulation have not yet been fully clarified. The present study examines whether serum citrate and ionized calcium levels affect whole blood clotting time in rats using the test tube method in which citrate is administered by rapid intravenous infusion. Citrate was infused via the tail vein into 10 rats at 3, 4 or 5 mmol/kg/hr for 1 hr, and then whole blood clotting time, serum citrate and ionized calcium levels were determined. Whole blood clotting time did not significantly change at citrate infusion rates of 3 and 4 mmol/kg/hr. However, at 5 mmol/kg/hr, whole blood clotting time was significantly prolonged by a factor of 2.1 relative to the untreated group, when the serum citrate level was 10.03 +/- 1.39 mmol/l (59.0-fold higher than that in the untreated group) and the serum-ionized calcium level was 0.29 +/- 0.02 mmol/l (0.2-fold lower than that in the untreated group). These results suggest that whole blood clotting time is significantly prolonged in rats with severe ionized hypocalcemia.

Tolerable infusion rate of citrate based on clinical signs and the electrocardiogram in conscious dogs.

BACKGROUND & AIMS: The possible clinical significance of the toxic effects of citrate has not yet been fully clarified. This study was therefore conducted to confirm the toxicity and determine the tolerable infusion rate of citrate administered by rapid intravenous infusion to conscious dogs. METHODS: Citrate solutions were infused via the cephalic vein of 4 conscious dogs at 0.33, 0.67, or 1.33mmol/kg/h up to 1.33mmol/kg. Clinical signs and the electrocardiogram were observed during and after infusion. Serum citrate and ionized calcium levels were also measured. RESULTS: Although the mean citrate level increased in accordance with the infusion rate, the calcium level decreased. No significant changes in clinical signs or the electrocardiogram were observed during infusion at 0.33mmol/kg/h despite an increase in the serum citrate level to 1.22+/-0.11mmol/l (pre-infusion value: 0.38+/-0.01mmol/l) and a decrease in the serum calcium level to 1.28+/-0.03mmol/l (pre-infusion value: 1.50+/-0.05mmol/l). Vomiting and QTc prolongation were observed at 0.67mmol/kg/h or higher. Salivation and tachycardia were observed at 1.33mmol/kg/h. CONCLUSIONS: Based on clinical signs and the electrocardiogram, the tolerable infusion rate of citrate in conscious dogs is concluded to be 0.33mmol/kg/h.

Maximum acceptable infusion rate of citrate: relationship between blood ionized calcium levels and cardiovascular effects in anesthetized rats.

BACKGROUND & AIMS: Citrate is a useful chemical as a stabilizer for infusion solutions. However, cardiovascular depression associated with ionized hypocalcemia has been observed during massive transfusion of citrated blood products. The goal of the present study was to determine the maximum acceptable infusion rate of citrate and safe blood ionized calcium (Ca(2+)) levels. METHODS: Citrate was administered intravenously to anesthetized rats at infusion rates between 0.5 and 2.0 mmol/kg/h for 4 h. Changes in heart rate (HR), arterial blood pressure, and the concentrations of plasma citrate and blood Ca(2+) were measured. RESULTS: Infusion of citrate caused decreases in arterial blood pressure and HR, but no severe cardiovascular depression was observed at infusion rates up to 1.0 mmol/kg/h. Plasma citrate levels reached a steady state within 1 h after the start of infusion at up to 1.0 mmol/kg/h. The concentrations of plasma citrate and blood Ca(2+) were 1.35 and 0.89 mmol/l, respectively, 4h after the start of infusion at 1.0 mmol/kg/h. CONCLUSIONS: The maximum acceptable infusion rate of citrate was 1.0 mmol/kg/h in anesthetized rats, and no severe cardiovascular effects were observed when the blood Ca(2+) level was 0.89 mmol/l or above.