Fukuda Tatsuru, Toyoshima Shigeki, Nakashima Yoshifumi, Koshitani Osamu, Kawaguchi Yoshiro, Momii Akira
Division of Pharmacology, Drug Safety and Metabolism, Otsuka Pharmaceutical Factory, Inc., Naruto, Tokushima 772-8601, Japan.
Clin Nutr. 2006 Dec;25(6):984-93. doi: 10.1016/j.clnu.2006.01.011. Epub 2006 May 15.
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.
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.
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.
Based on clinical signs and the electrocardiogram, the tolerable infusion rate of citrate in conscious dogs is concluded to be 0.33mmol/kg/h.
枸橼酸盐毒性作用的潜在临床意义尚未完全阐明。因此，本研究旨在证实其毒性，并确定在清醒犬中快速静脉输注枸橼酸盐时的可耐受输注速率。
通过头静脉向4只清醒犬输注枸橼酸盐溶液，输注速率分别为0.33、0.67或1.33mmol/kg/h，直至剂量达1.33mmol/kg。在输注期间及之后观察临床症状和心电图。同时测定血清枸橼酸盐和离子钙水平。
尽管平均枸橼酸盐水平随输注速率增加而升高，但钙水平降低。在以0.33mmol/kg/h的速率输注时，尽管血清枸橼酸盐水平升高至1.22±0.11mmol/L（输注前值：0.38±0.01mmol/L），血清钙水平降低至1.28±0.03mmol/L（输注前值：1.50±0.05mmol/L），但在输注期间未观察到临床症状或心电图有显著变化。在0.67mmol/kg/h及更高输注速率时观察到呕吐和QTc延长。在1.33mmol/kg/h时观察到流涎和心动过速。
基于临床症状和心电图，得出清醒犬中枸橼酸盐的可耐受输注速率为0.33mmol/kg/h。
