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To investigate the efficacy of esmolol in protecting the myocardium from ischemia during pediatric cardiac surgery.Esmolol, an ultra-short acting beta 1-adrenoceptor blocker, reduces myocardial injury in adult cardiac operations. However, this technique is rarely used in pediatric cardiac surgery.Thirty children with ventricular septal defect were randomly allocated to the esmolol group and the control group. Patients received intravenous esmolol (0.05 mg·kg−1·min−1 after tracheal intubation, 0.3 mg·kg−1·min−1 during cardiopulmonary bypass (CPB) and 0.03–0.05 mg·kg−1·min−1 until the end of surgery) or placebo, respectively.Plasma levels of creatine kinase-MB, cardiac troponin I in the esmolol group 2 min after completion of CPB, at the end of surgery, 4 h after surgery, and the first postoperative day were significantly lower than those in the control group. Values of heart rate 10 min after induction, 2 min before institution of CPB, 2 min after completion of CPB, and at the end of surgery were significantly lower in the esmolol group; however, mean arterial pressure, CPB time, cross-clamp time, and the rate of heart spontaneous rebeating were not statistically different between two groups. Cumulative postoperative dosage of dopamine in the esmolol group (100.1 ± 53.1 mg) was significantly less than that in the control group (171.4 ± 92.1 mg).Esmolol can protect the myocardium from ischemic injury during CPB in children and significantly reduce the use of inotropic drug.