Esmolol has been used to improve hemodynamic stability during sternotomy and aortic manipulation for coronary artery bypass graft surgery. In order to investigate the alterations of esmolol metabolism by hypothermic cardiopulmonary bypass (CPB), the effect of temperature on the metabolism of esmolol in vitro was determined. Samples of human whole blood were combined with esmolol solution (50 micrograms/mL in 0.9 mol/L NaCl) and incubated at 4 degrees C, 15 degrees C, 25 degrees C, and 37 degrees C. Aliquots were sampled at 1, 5, 10, 15, 30, 60, and 120 minutes; esmolol concentration was determined using high-pressure liquid chromatography. There was a temperature-dependent decrease in the degradation of esmolol. The half-life for esmolol in human blood was 19.6 +/- 3.8 minutes at 37 degrees C, 47 +/- 10.1 minutes at 25 degrees C, 152 +/- 46.6 minutes at 15 degrees C, and 226.7 +/- 60.1 minutes at 4 degrees C. This study clearly shows marked reduction of esmolol metabolism with hypothermia possibly leading to persistent beta-adrenergic blockade following the discontinuation of CPB. Persistent beta-blockade may provide additional protection to the ischemic myocardium during hypothermic arrest and/or result in difficulty in weaning from CPB.