Maximum acceptable infusion rate of citrate: relationship between blood ionized calcium levels and cardiovascular effects in anesthetized rats.
OBJECTIVE
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.
Toyoshima
Shigeki
S
Division of Pharmacology, Drug Safety and Metabolism, Otsuka Pharmaceutical Factory, Inc., 115 Kuguhara, Naruto, Tokushima 772-8601, Japan. toyosisg@otsukakj.co.jp
Fukuda
Tatsuru
T
Masumi
Shigeru
S
Nakashima
Yoshifumi
Y
Kawaguchi
Yoshiro
Y
Nakayama
Mitsuo
M
D000818:Animals; D019540:Area Under Curve; D001794:Blood Pressure / Q000187:drug effects*; D002118:Calcium / Q000097:blood*; D002614:Chelating Agents / Q000378:metabolism / Q000493:pharmacokinetics*; D019343:Citric Acid / Q000097:blood / Q000493:pharmacokinetics*; D004305:Dose-Response Relationship, Drug; D006339:Heart Rate / Q000187:drug effects*; D006801:Humans; D006996:Hypocalcemia / Q000139:chemically induced; D007262:Infusions, Intravenous; D008297:Male; D011897:Random Allocation; D051381:Rats
D002614:Chelating Agents; D019343:Citric Acid; D002118:Calcium