Sung R J, Blanski L, Kirshenbaum J, MacCosbe P, Turlapaty P, Laddu A R
J Clin Pharmacol. 1986 Mar;26(S1):A15-A26. doi: 10.1002/j.1552-4604.1986.tb02983.x.
The efficacy and safety of esmolol, an ultra-short-acting beta-adrenergic blocking agent (elimination half-life, 9 min), was investigated in 358 patients with supraventricular tachyarrhythmias (SVTs) in three multicenter studies (placebo-controlled, propranolol-controlled, and open-label baseline-controlled) and in 19 patients with myocardial ischemia (acute myocardial infarction or unstable angina) in a single-center, open-label study. Esmolol was infused intravenously in doses ranging from 25 micrograms/kg/min to 300 micrograms/kg/min. In SVT studies, efficacy was judged by one or more of the following: a reduction of at least 15% to 20% from the average baseline heart rate, heart rate less than 100 beats/min, or conversion to normal sinus rhythm (NSR). Results revealed that esmolol was superior to placebo and equal to propranolol in controlling heart rate in SVT patients. Conversion to NSR was comparable in patients treated with esmolol (14%) and in those treated with propranolol (16%). The majority of patients achieved therapeutic response at esmolol doses of 200 micrograms/kg/min or less. Among esmolol-treated patients, recovery from beta blockade (i.e., heart rate approaching baseline levels) was achieved within ten minutes after discontinuation of infusion, indicating a brief duration of action of esmolol. In contrast, beta blockade persisted 4.5 hours after discontinuation of propranolol. In patients with myocardial ischemia, esmolol effectively reduced heart rate and blood pressure, thereby decreasing rate-pressure product. The most frequent adverse effect in patients treated with esmolol was hypotension. No clinically significant laboratory abnormalities were reported in esmolol-treated patients. Esmolol was well tolerated in patients infused for durations of up to 24 hours and in patients with conditions for which treatment with beta blockers is inappropriate. These results suggest that esmolol effectively and rapidly controls the heart rate in patients with SVT and in patients with acute myocardial ischemia. Furthermore, because of its short half-life, esmolol offers excellent benefits as compared with the currently available beta-adrenergic blockers in the treatment of critically ill patients. Esmolol was well tolerated by patients for whom beta blockers in general would be unsuitable.
在三项多中心研究(安慰剂对照、普萘洛尔对照及开放标签基线对照)中,对358例室上性快速心律失常(SVT)患者,以及在一项单中心开放标签研究中,对19例心肌缺血(急性心肌梗死或不稳定型心绞痛)患者,研究了超短效β肾上腺素能阻滞剂艾司洛尔(消除半衰期9分钟)的疗效和安全性。艾司洛尔静脉输注剂量范围为25微克/千克/分钟至300微克/千克/分钟。在SVT研究中,疗效通过以下一项或多项判断:平均基线心率降低至少15%至20%、心率低于100次/分钟或转为正常窦性心律(NSR)。结果显示,在控制SVT患者心率方面,艾司洛尔优于安慰剂且与普萘洛尔相当。艾司洛尔治疗患者转为NSR的比例(14%)与普萘洛尔治疗患者(16%)相当。大多数患者在艾司洛尔剂量为200微克/千克/分钟或更低时达到治疗反应。在接受艾司洛尔治疗的患者中,输注停止后十分钟内β受体阻滞作用恢复(即心率接近基线水平),表明艾司洛尔作用持续时间较短。相比之下,普萘洛尔停药后β受体阻滞作用持续4.5小时。在心肌缺血患者中,艾司洛尔有效降低心率和血压,从而降低心率血压乘积。接受艾司洛尔治疗的患者最常见的不良反应是低血压。接受艾司洛尔治疗的患者未报告有临床意义的实验室异常。艾司洛尔在输注长达24小时的患者以及β受体阻滞剂治疗不适用的疾病患者中耐受性良好。这些结果表明,艾司洛尔能有效且迅速地控制SVT患者及急性心肌缺血患者的心率。此外,由于其半衰期短,与目前可用的β肾上腺素能阻滞剂相比,艾司洛尔在治疗重症患者方面具有显著优势。艾司洛尔在一般β受体阻滞剂不适用的患者中耐受性良好。