Background: Cephazolin and vancomycin are commonly used for antibiotic prophylaxis during surgery supported by cardiopulmonary bypass (CPB). Antibiotic pharmacokinetics (PK) can be altered by CPB through haemodilution, haemofiltration, hypothermia and drug adsorption to the circuitry (1). Adsorption can contribute to decreased antibiotic concentrations with consequent reduced prophylactic effectiveness (2). Highly protein bound drugs like cephazolin can have substantial adsorption to CPB machine circuitry (3). An ex vivo benchtop study was conducted to investigate possible cephazolin and vancomycin adsorption.
Objective: To quantify cephazolin and vancomycin adsorption to the CPB machine circuitry.
Methods: Enclosed CPB machines (not connected to a patient) were primed with either whole blood or crystalloid solutions. Cephazolin, vancomycin or a combination, was administered into the circuit and samples taken at regular intervals over 1 hour. Twelve experimental runs were conducted using different CPB machine sizes (neonate to adult), priming solutions, cardioplegia volumes and temperature changes. Unbound concentrations of cephazolin and vancomycin were quantified using high performance liquid chromatography. Data analysis was performed using NONMEM 7.4.3.
Results: Antibiotic concentrations in 300 samples were quantified. A two compartment distribution model was used to describe antibiotic adsorption. The amount of drug remaining in the adsorption compartment at the end of the experimental runs indicated that cephazolin was substantially adsorbed whereas this effect was small with vancomycin (Table 1). Neonatal sized circuits showed the most adsorption of antibiotic which is likely due to the greater circuit surface area to pump priming volume ratio.
Table 1 – Average drug amount remaining in adsorption compartment at end of the experimental run for each circuit size.
|
Circuit size |
Cephazolin |
Vancomycin |
|
Neonate |
22.3% |
9.6% |
|
Paediatric (infant) |
12.1% |
– |
|
Child |
7.8% |
0.8% |
|
Adult |
3.1% |
0.3% |
Conclusion: Antibiotic adsorption to CPB circuitry can explain some of variability in drug concentrations. The model for cephazolin adsorption can be incorporated into a population PK model in patients supported by CPB.
References
1. Sherwin J, Heath T, Watt K. Pharmacokinetics and dosing of anti-infective drugs in patients on extracorporeal membrane oxygenation: a review of the current literature. Clinical therapeutics. 2016 Sep 1;38(9):1976-94.
2. Zeilmaker‐Roest GA, van Saet A, van Hoeven MP, Koch BC, van Rosmalen J, Kinzig M, Söergel F, Wildschut ED, Stolker RJ, Tibboel D, Bogers AJ. Recovery of cefazolin and clindamycin in in vitro pediatric CPB systems. Artificial Organs. 2020 Apr;44(4):394-401.
3. Shekar K, Roberts JA, Mcdonald CI, Ghassabian S, Anstey C, Wallis SC, Mullany DV, Fung YL, Fraser JF. Protein-bound drugs are prone to sequestration in the extracorporeal membrane oxygenation circuit: results from an ex vivo study. Critical Care. 2015 Dec 1;19(1):164.