Factors affecting ceftriaxone plasma protein binding during open heart surgery.

Factors most likely contributing to reduced ceftriaxone plasma protein binding in patients undergoing open heart surgery (OHS) were examined. Binding was determined by equilibrium dialysis. It was found that ceftriaxone does not bind significantly to red blood cells, alpha 1-acid glycoprotein, or to protamine, and that the pH of serum did not significantly affect binding. Albumin is the major protein to bind ceftriaxone, and binding decreases with lower albumin concentrations due to fewer binding sites. The binding of ceftriaxone was not affected by the in vitro addition of heparin or methylprednisolone, but high concentrations of methylprednisolone hemisuccinate increased the free fraction of ceftriaxone. Increased concentrations of free fatty acids (FFA) were demonstrated in several patients undergoing OHS. The in vitro addition of palmitic, stearic, linoleic, and oleic acids in high concentrations decreased the binding of ceftriaxone. Ceftriaxone binding in patient samples correlated with the molar ratio of FFA to albumin, but not to either individually. The dual effect of increased FFA and decreased albumin concentrations in OHS patients appears responsible for most of the observed binding alterations.