Dobutamine pharmacokinetics during dobutamine stress echocardiography

Many patients fail to achieve target heart rate during dobutamine stress echocardiography (DSE). We evaluated the pharmacokinetics of dobutamine during DSE to determine whether patients with an impaired chronotropic response have higher rates of dobutamine clearance and consequently relatively lower plasma dobutamine levels. Plasma dobutamine levels, heart rate, and left ventricular (LV) ejection fraction (EF) were measured in 13 male patients referred for DSE at baseline and at the end of stepped 3-minute dobutamine infusions of 5, 10, 20, and 30 microg/kg/min. Dobutamine levels increased with doses: 27 +/- 10, 111 +/- 17, 275 +/- 17, and 403 +/- 28 ng/ml (mean +/- SEM). There was no relation observed between the plasma dobutamine level achieved at the 30-microg infusion dose and the increase in heart rate from baseline (r = 0.066; p = 0.83). Baseline LVEF and a measure of chronotropic beta responsivity were identified as independent predictors of dobutamine clearance, together accounting for 73% of the variance in dobutamine clearance. In conclusion, (1) there is a dose-dependent increase in plasma dobutamine levels during DSE, (2) dobutamine clearance is positively related to baseline LVEF and is partially mediated by a beta-receptor mechanism, and (3) an impaired chronotropic response during DSE is not due to failure to achieve a sufficiently high dobutamine level. We conclude that in patients who lack an adequate heart rate response during the early stages of DSE (e.g., up to 20 microg/kg/min infusion), administration of atropine rather than progressively higher amounts of dobutamine may provide a more effective strategy to achieve target heart rate.