Pharmacokinetic analysis of cloxacillin loss in children undergoing major surgery with massive bleeding

Abstract

To determine the magnitude of cloxacillin loss during surgical procedures involving significant blood loss and high fluid replacement, we compared the pharmacokinetics of cloxacillin in children during craniomaxillofacial surgery with the disposition of the drug in healthy young adult volunteers with intact circulation. Blood loss during craniofacial operations may exceed blood volume, in some cases by as much as three times. Hemodynamic replacement with electrolyte solutions and blood products, which do not contain the drug, further dilute cloxacillin concentrations. In the patients that we studied, mean drug loss was estimated at 71%. Cloxacillin concentrations in serum fell below the lower range of the MIC for Staphylococcus aureus during significant portions of the surgical procedures. Thus, the traditional dosing of cloxacillin during prolonged operations with massive blood loss is inadequate. A more frequent dosing interval or priming of all replacement fluids with the drug may be required to maintain therapeutic levels. Our findings suggest that massive blood loss is likely to have a dramatic effect on the level of any drug with a small distribution volume. If such a drug is essential to the patient's well-being (e.g., antibiotics, antiarrhythmics, and anticonvulsants), it must be replaced promptly.