Effective Dose of Landiolol, an Ultra-Short-Acting β-Blocker, to Decrease Heart Rate During On-Pump, Beating Coronary Artery Bypass Grafting

Abstract

Decreasing the heart rate (HR) using landiolol, an ultra-short-acting β-blocker, is helpful for completing a meticulous distal anastomosis during on-pump or off-pump, beating coronary artery bypass grafting (CABG) surgery. We determine the effectiveness of landiolol to decrease the HR because the most effective dose has not been established. Observational open-label pharmacodynamics cohort study. Single center, Hamamatsu University Hospital. 28 patients undergoing on-pump, beating CABG. Landiolol 5 μg/kg/min was started (time 0) and then increased to 15, 25, and 35 μg/kg/min at 10-min intervals during left internal thoracic artery (LITA) to left anterior descending artery (LAD) anastomosis. Pharmacodynamics were characterized using a sigmoidal inhibitory maximum effect model to determine the percent decrease in HR according to the landiolol dose. Baseline (mean ± SD) HR (85 ± 10 beats/min) decreased to 81 ± 9, 71 ± 10, 67 ± 9, and 67 ± 9 beats/min, respectively, at the four landiolol infusion points evaluated. Estimated maximum percent decrease in HR from the baseline effective dose value (ED0) was -21.5 (-25.3 to -17.8) [mean (95% confidence interval)]%. ED50, ED90, and ED95 were 9.5 (9.0-10.1), 25.0 (22.5-27.6), and 35.2 (30.3-40.1) μg/kg/min, respectively. Landiolol maximally decreased HR just over 20% of the baseline HR. Hence, landiolol 25 μg/kg/min is likely a sufficient dose during LITA-LAD anastomosis during on-pump, beating CABG.