Influence of Hemodynamic Variations on the Pharmacokinetics of Landiolol in Patients Undergoing Cardiovascular Surgery

Abstract

Although landiolol is useful in the emergency management of atrial fibrillation, atrial flutter, and tachycardia, as well as in perioperative arrhythmia control, the influence of hemodynamic changes on the pharmacokinetics of landiolol is unknown. We investigated the influence of hemodynamic variation and the following hepatocirculatory changes after systemic heparinization on the pharmacokinetics of landiolol in patients undergoing cardiovascular surgery under cardiopulmonary bypass. Cardiac output and cardiac index (CI) were continuously monitored in 19 patients using an arterial pressure-based cardiac output monitor. The middle and right hepatic venous blood flow indexes (mHVBFI and rHVBFI) were measured by transesophageal echocardiography, and hemodynamic data were collected at points (T1-T3) as follows: T1, before administration of heparin and after sternotomy; T2, just before systemic heparinization (300 U/kg); T3, 10 min after T2. The plasma concentration of landiolol was measured by HPLC at the same point. After administration of heparin, mean arterial blood pressure, CI, mHVBFI, and rHVBFI were significantly decreased (<0.05). Heart rate was not significantly changed. After systemic heparinization, the landiolol concentration was significantly decreased from 0.407±0.251 µg·mL(-1) to 0.232±0.207 µg·mL(-1) (<0.01). There was no significant difference between T1 and T2 (=0.88). In conclusion, the plasma concentration of landiolol was decreased by diminished CI due to systemic heparinization, but not affected by the change of hepatic blood flow.