Pharmacokinetic Assessment of Pre- and Post-Oxygenator Vancomycin Concentrations in Extracorporeal Membrane...

Extracorporeal membrane oxygenation (ECMO) is a form of cardiopulmonary life support frequently utilized in catastrophic lung and or cardiac failure. Patients on ECMO often receive vancomycin therapy for treatment or prophylaxis against Gram-positive organisms. It is unclear if ECMO affects vancomycin pharmacokinetics, thus we modeled the pharmacokinetic behavior of vancomycin according to ECMO-specific variables.

Adult patients receiving vancomycin and Veno-Arterial-ECMO between 12/1/2016 and 10/1/2017 were prospectively enrolled. Extracorporeal membrane oxygenation settings and four sets of pre- and post-oxygenator vancomycin concentrations were collected for each patient. Compartmental models were built and assessed ECMO flow rates on vancomycin clearance and potential circuit sequestration. Bayesian posterior concentrations of the pre- and post-oxygenator concentrations were obtained for each patient, and summary pharmacokinetic parameters were calculated. Simulations were performed from the final model for efficacy and toxicity predictions.

Eight patients contributed 64 serum concentrations. Patients were a median (interquartile range) age of 58.5 years (50.8-62.3) with a calculated creatinine clearance of 39 mL/min (29.5-62.5) and ECMO flow rates of 3980 mL/min (interquartile range = 3493.75-4132.5). A three-compartment model best fit the data (Bayesian: plasma pre-oxygenation R² = 0.99, post-oxygenation R² = 0.99). Vancomycin clearance was not impacted by ECMO flow rate (p = 0.7). Simulations demonstrated that vancomycin 1 g twice daily was rarely sufficient for minimum inhibitory concentrations > 0.5 mg/L. Doses ≥ 1.5 g twice daily often exceeded toxicity thresholds for exposure.

Extracorporeal membrane oxygenation flow rates did not influence vancomycin clearance between flow rates of 3500 and 5000 mL/min and vancomycin was not sequestered in ECMO. Common vancomycin regimens resulted in suboptimal efficacy and/or excessive toxicity. Individual therapeutic drug monitoring is recommended for patients on ECMO.