What is known and objective: The influence of venovenous extracorporeal membrane oxygenation (VV-ECMO) on the population pharmacokinetics (PPK) of vancomycin in recipients after lung transplantation (LTx) is unknown. We investigated whether VV-ECMO influences vancomycin PPK and determined optimal recommended dosage for patients after LTx.
Methods: We tested vancomycin serum concentration and calculated PPK parameters using NONMEM. To check for any potential influence of ECMO on vancomycin PK, we compared ECMO patients with a non-ECMO patient control group, and patients before and after ECMO weaning as self-control to analysed changes in vancomycin PK. Monte Carlo dosing simulation was conducted to explore vancomycin dosing regimens.
Results: Nineteen ECMO and 6 non-ECMO lung transplant recipients were enrolled. Vancomycin serum concentrations did not significantly differ between patients with and without ECMO support. Comparison of separate vancomycin population pharmacokinetic models showed that ECMO patients had smaller peripheral compartment volume of distribution (V2 ) [Estimate (relative standard error, RSE, %) 19.7 (12) vs. 22 (17) L, P = .003] than non-ECMO patients. For treatment of methicillin-resistant Staphylococcus aureus (MRSA) infections with MIC ≤ 0.5 µg/mL, venous infusion of 400 mg vancomycin every 8 hours was recommended. For MRSA infection with MIC ≤ 1 µg/mL, the proposed dosage was 600 mg every 8 hours.
What is new and conclusion: Venovenous extracorporeal membrane oxygenation slightly alters vancomycin PK but does not significantly impact vancomycin serum concentration in patients after LTx. Dose adjustment is not necessary for VV-ECMO support. Specific vancomycin dosing regimens with lower nephrotoxicity may benefit LTx recipients with VV-ECMO.
Keywords: lung transplantation; population pharmacokinetics; vancomycin; venovenous extracorporeal membrane oxygenation.
© 2020 John Wiley & Sons Ltd.