Dobutamine pharmacodynamics during dobutamine stress echocardiography and the impact of β-blocker withdrawal: A report from the women's ischemic syndrome evaluation study

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Journal Article

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Study Objectives. To determine the pharmacodynamic parameters of dobutamine during dobutamine stress echocardiography (DSE) and to determine how β-blocker withdrawal the evening before DSE affects responses to dobutamine during DSE. Design. Retrospective analysis. Setting. University medical center. Patients. One hundred thirty-six women who had chest pain or other symptoms suggestive of myocardial ischemia and were considered to have a clinical indication for coronary angiography. Measurements and Main Results. Patients underwent DSE with dobutamine dosages titrated from 5 to 40 pg/kg/minute. The infusion was terminated if the patient reached target heart rate or symptoms developed. Those taking β-blockers withheld their doses the evening before DSE. Traditional pharmacodynamic modeling revealed a wide range in responses to dobutamine. Data for 62% of patients not taking β-blockers were described by the Emax (maximum heart rate response to dobutamine) model, whereas data for only 39% of patients taking β-blockers were best described by this model (p=0.01). Patients taking β-blockers also had a smaller mean increment in left ventricular ejection fraction (10.8% ± 4.2% vs 14.1% ± 9.3%, p<0.01), a trend toward a higher ED50 (dobutamine dosage rate causing half the maximum heart-rate response; median 16.8 pg/kg/min, p=0.12) and a lower sigmoidicity factor determining the shape of the curve (median 2.1, p=0.03). Conclusion. The response to dobutamine exhibits wide interpatient variability, even in the absence of β-blockade. Nonetheless, in the absence of β-blockers, in most patients the dobutamine response reaches a plateau by the time the maximum infusion rate (40 pg/kg/min) is reached. Withdrawal of β-blockers the evening before DSE may be inadequate time for elimination of β-blocker effect, requiring the addition of atropine to achieve the desired response during DSE.