Dobutamine pharmacodynamics during dobutamine stress echocardiography and the impact of beta-blocker withdrawal: a report from the Women's Ischemic Syndrome Evaluation Study.
OBJECTIVE
To determine the pharmacodynamic parameters of dobutamine during dobutamine stress echocardiography (DSE) and to determine how beta-blocker withdrawal the evening before DSE affects responses to dobutamine during DSE.


METHODS
Retrospective analysis.


METHODS
University medical center.


METHODS
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


RESULTS
Patients underwent DSE with dobutamine dosages titrated from 5 to 40 microg/kg/minute. The infusion was terminated if the patient reached target heart rate or symptoms developed. Those taking beta-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 beta-blockers were described by the Emax (maximum heart rate response to dobutamine) model, whereas data for only 39% of patients taking beta-blockers were best described by this model (p = 0.01). Patients taking beta-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 microg/kg/min, p = 0.12) and a lower sigmoidicity factor determining the shape of the curve (median 2.1, p = 0.03).


CONCLUSIONS
The response to dobutamine exhibits wide interpatient variability, even in the absence of beta-blockade. Nonetheless, in the absence of beta-blockers, in most patients the dobutamine response reaches a plateau by the time the maximum infusion rate (40 microg/kg/min) is reached. Withdrawal of beta-blockers the evening before DSE may be inadequate time for elimination of beta-blocker effect, requiring the addition of atropine to achieve the desired response during DSE.
Humma
Larisa M
LM
Department of Pharmacy Practice, University of Florida, Gainesville 32610-0486, USA.
Richardson
Heather E
HE
Lewis
Jannet F
JF
McGorray
Susan P
SP
Pepine
Carl J
CJ
Johnson
Julie A
JA
D000319:Adrenergic beta-Antagonists / Q000494:pharmacology* / Q000627:therapeutic use; D004280:Dobutamine / Q000494:pharmacology*; D025401:Echocardiography, Stress / Q000187:drug effects*; D005260:Female; D006339:Heart Rate / Q000187:drug effects; D006785:Hospitals, University; D006801:Humans; D017202:Myocardial Ischemia / Q000000981:diagnostic imaging* / Q000188:drug therapy / Q000503:physiopathology; D012189:Retrospective Studies; D013375:Substance Withdrawal Syndrome
D000319:Adrenergic beta-Antagonists; D004280:Dobutamine