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

• Published in: Clinical nutrition (Edinburgh, Scotland) Vol. 25; no. 6; pp. 984 - 993
• Main Authors: Fukuda, Tatsuru, Toyoshima, Shigeki, Nakashima, Yoshifumi, Koshitani, Osamu, Kawaguchi, Yoshiro, Momii, Akira
• Format: Journal Article
• Language: English
• Published: Kidlington Elsevier Ltd 01.12.2006; Elsevier
• Subjects: Animals; Anticoagulants - pharmacokinetics; Anticoagulants - toxicity; Area Under Curve; Biological and medical sciences; Calcium - blood; Citrate infusion; Citric Acid - pharmacokinetics; Citric Acid - toxicity; Clinical signs; Dog; Dogs; Dose-Response Relationship, Drug; Electrocardiogram; Electrocardiography; Epidemiology; General aspects; Hypocalcemia; Hypocalcemia - chemically induced; Infusions, Intravenous; Ionized calcium; Long QT Syndrome - chemically induced; Magnesium - blood; Male; Medical sciences; Metabolic diseases; Public health. Hygiene; Public health. Hygiene-occupational medicine; Random Allocation; Salivation; Tachycardia - chemically induced; Time Factors; Vomiting - chemically induced; Ionized calcium; Citrate infusion; Dog; Electrocardiogram; Hypocalcemia; Clinical signs; Fissipedia; Carnivora; Nutrition; Rate; Citrate; Epidemiology; Electrodiagnosis; Vertebrata; Mammalia; Perfusion; Animal; Electrocardiography
• ISSN: 0261-5614; 1532-1983
• DOI: 10.1016/j.clnu.2006.01.011

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 1.33 mmol/kg/h up to 1.33 mmol/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 0.33 mmol/kg/h despite an increase in the serum citrate level to 1.22±0.11 mmol/l (pre-infusion value: 0.38±0.01 mmol/l) and a decrease in the serum calcium level to 1.28±0.03 mmol/l (pre-infusion value: 1.50±0.05 mmol/l). Vomiting and QTc prolongation were observed at 0.67 mmol/kg/h or higher. Salivation and tachycardia were observed at 1.33 mmol/kg/h. Based on clinical signs and the electrocardiogram, the tolerable infusion rate of citrate in conscious dogs is concluded to be 0.33 mmol/kg/h.