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Anesthesiology:
doi: 10.1097/ALN.0000000000000408
Perioperative Medicine: PDF Only

An Enantiomerically Pure Formulation of Esmolol Attenuates Hypotension and Preserves Heart Rate Control in Dogs.

McKee, Jeffrey S. Ph.D., D.A.B.T.; Rabinow, Barrett E. Ph.D.; Daller, Justin R. B.S.; Brooks, Benjamin D. M.S.; Baumgartner, Bernhard D.V.M.; Rohatgi, Priyanka Ph.D.

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Abstract

Background: Esmolol is marketed as a racemate (RS-esmolol) with hypotension being the most frequently reported adverse event. Previously, it has been shown that the S-enantiomer (S-esmolol) possesses all of the heart rate (HR) control. The authors studied whether S-esmolol alone mitigates hypotension at similar degrees of HR control compared with RS-esmolol.
Methods: The effects of RS- and S-esmolol on blood pressure (BP) were compared at multiple infusion rates producing similar HR control in dogs (N = 21). Differences in BP were further interrogated by monitoring global cardiovascular function and included the R-enantiomer (R-esmolol) (N = 3).
Results: S-esmolol at half the rate ([mu]g kg-1 min-1) of RS-esmolol provided the same degree of HR control over all infusion rates. RS-esmolol lowered BP by 3, 6, 11, 20, and 38 mmHg at 90, 300, 600, 1,000, and 2,000 [mu]g kg-1 min-1, compared with 2, 4, 5, 10, and 16 mmHg at 45, 150, 300, 500, and 1,000 [mu]g kg-1 min-1 for S-esmolol. Decreased BP with RS-esmolol was attributed to decreases in left ventricular developed pressure (LVDP) (-34 mmHg), LVdP/dt+max (-702 mmHg/s), and cardiac output (-1 l/min). R-esmolol also decreased BP (-10 mmHg), LVDP (-10 mmHg), LVdP/dt+max (-241 mmHg/s), and cardiac output (to -0.2 l/min). S-esmolol reversed these trends toward pre-esmolol values by increasing BP (+13 mmHg), LVDP (+12 mmHg), LVdP/dt+max (+76 mmHg/s), and cardiac output (+0.4 l/min).
Conclusions: R-enantiomer provided no HR control, but contributed to the hypotension with RS-esmolol, which appears to be due to negative inotropy. Thus, an S-enantiomer formulation of esmolol may provide similar HR control with less hypotension.
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