- Background: The inotropic drug levosimendan is often used off-label perioperatively in cardiac surgery patients with cardiopulmonary bypass (CPB). Data regarding serum concentrations of levosimendan and its metabolites within this context is lacking.
Methods: Total serum concentrations (TSC) and unbound fractions (UF) of levosimendan and its metabolites OR-1896 and OR-1855 in cardiac surgery patients with CPB were retrospectively measured using LC-ESI-MS/MS. Simulation of expected levosimendan TSC was performed using Pharkin 4.0. Serum NT-proBNP was assessed with ELISA.
Results: After prolonged levosimendan infusion (1.25 mg or 2.5 mg, respectively) after induction of anaesthesia, a median TSC of 1.9 ng/ml and 10.4 ng/ml was determined in samples taken directly after surgery (T1). Median TSC of 7.6 ng/ml and 22.0 ng/ml, respectively, were simulated at T1. Whereas 1.1 ng/ml and 1.6 ng/ml TSC of OR-1896, respectively, was quantified the day after surgery (T2), TSC of theBackground: The inotropic drug levosimendan is often used off-label perioperatively in cardiac surgery patients with cardiopulmonary bypass (CPB). Data regarding serum concentrations of levosimendan and its metabolites within this context is lacking.
Methods: Total serum concentrations (TSC) and unbound fractions (UF) of levosimendan and its metabolites OR-1896 and OR-1855 in cardiac surgery patients with CPB were retrospectively measured using LC-ESI-MS/MS. Simulation of expected levosimendan TSC was performed using Pharkin 4.0. Serum NT-proBNP was assessed with ELISA.
Results: After prolonged levosimendan infusion (1.25 mg or 2.5 mg, respectively) after induction of anaesthesia, a median TSC of 1.9 ng/ml and 10.4 ng/ml was determined in samples taken directly after surgery (T1). Median TSC of 7.6 ng/ml and 22.0 ng/ml, respectively, were simulated at T1. Whereas 1.1 ng/ml and 1.6 ng/ml TSC of OR-1896, respectively, was quantified the day after surgery (T2), TSC of the intermediate metabolite OR-1855 was mostly below the lower limit of quantification (LLOQ). The UF was 0.5% and 1.1% for levosimendan and 64.1% and 52.1% for OR-1896, respectively, with over half the samples being below LLOQ. No difference in NT-proBNP concentrations before surgery and T2 was detected.
Discussion: The low TSC, UF and unchanged NT-proBNP levels suggest a need for dose adjustments of levosimendan in this off-label range. In addition, the differences between the measured and estimated concentrations may suggest a possible influence of a CPB on levosimendan serum concentrations. Due to high variation of serum levels between patients, an optimized dosing regimen combined with therapeutic drug monitoring may be advisable.…
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