Effect of Heart Rate Control With Esmolol on Hemodynamic and Clinical Outcomes in Patients With Septic Shock A Randomized Clinical Trial
Effect of Heart Rate Control With Esmolol on Hemodynamic and Clinical Outcomes in Patients With Septic Shock A Randomized Clinical Trial
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DOI：
10.1001/jama.2013.278477
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发表时间：
2013-10-23
影响因子：
120.7
通讯作者：
Singer, Mervyn
中科院分区：
文献类型：
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作者：
Morelli, Andrea;Ertmer, Christian;Singer, Mervyn
重要性-受体阻滞剂治疗可以控制心率和减轻-肾上腺素能受体刺激对感染性休克的有害影响。然而，β受体阻滞剂传统上不用于这种情况，并且可能通过负性肌力和降压作用加重心血管失代偿。目的探讨短效β受体阻滞剂艾司洛尔治疗严重感染性休克的疗效。设计、环境和患者：2010年11月至2012年7月在一所大学医院重症监护病房（ICU）进行的开放标签、随机2期研究，纳入心率为95/min或更高的感染性休克患者，需要大剂量去甲肾上腺素维持平均动脉压为65 mm Hg或更高。干预措施：我们随机分配77例患者在ICU住院期间接受持续滴注艾司洛尔，以维持心率在80 - 94/min之间，77例患者接受标准治疗。主要结局和测量我们的主要结局是通过96小时的艾司洛尔治疗将心率降低到95/min以下，并将心率维持在80 - 94/min之间。次要结局包括血液动力学和器官功能测量；24,48,72和96小时去甲肾上腺素剂量；以及随机分组后28天内发生的不良事件和死亡率。结果与对照组相比，艾司洛尔组所有患者均达到了目标心率。艾司洛尔组前96小时心率的中位AUC为-28/min (IQR， -37至-21)，对照组为-6/min (95% CI， -14至0)，平均降低18/min （P < 0.001）。对于卒中容量指数，艾司洛尔的中位AUC为4 mL/m(2) (IQR， -1至10)，对照组为1 mL/m(2) (IQR， -3至5，P = 0.02)，而艾司洛尔的左室卒中工作指数为3 mL/m(2) (IQR， -2至5)，对照组为1 mL/m(2) （IQR， -2至5，P = 0.03）。对于动脉性乳酸血症，艾司洛尔的中位AUC为-0.1 mmol/L (IQR, -0.6至0.2)，对照组为0.1 mmol/L (IQR, -0.3至0.6,P = 0.007)；去甲肾上腺素，艾司洛尔组为-0.11 β g/kg/min (IQR, -0.46 ~ 0.02)，对照组为-0.01 β g/kg/min (IQR, -0.2 ~ 0.44) （P = 0.003）。艾斯洛尔组降低了液体需要量：中位AUC为3975 mL/24 h (IQR， 3663至4200)，对照组为4425 mL/24 h （IQR， 4038至4775）
IMPORTANCE beta-Blocker therapy may control heart rate and attenuate the deleterious effects of beta-adrenergic receptor stimulation in septic shock. However, beta-Blockers are not traditionally used for this condition and may worsen cardiovascular decompensation related through negative inotropic and hypotensive effects.OBJECTIVE To investigate the effect of the short-acting beta-blocker esmolol in patients with severe septic shock.DESIGN, SETTING, AND PATIENTS Open-label, randomized phase 2 study, conducted in a university hospital intensive care unit (ICU) between November 2010 and July 2012, involving patients in septic shock with a heart rate of 95/min or higher requiring high-dose norepinephrine to maintain a mean arterial pressure of 65 mm Hg or higher.INTERVENTIONS We randomly assigned 77 patients to receive a continuous infusion of esmolol titrated to maintain heart rate between 80/min and 94/min for their ICU stay and 77 patients to standard treatment.MAIN OUTCOMES AND MEASURES Our primary outcomewas a reduction in heart rate below the predefined threshold of 95/min and to maintain heart rate between 80/min and 94/min by esmolol treatment over a 96-hour period. Secondary outcomes included hemodynamic and organ function measures; norepinephrine dosages at 24, 48, 72, and 96 hours; and adverse events and mortality occurring within 28 days after randomization.RESULTS Targeted heart rateswere achieved in all patients in the esmolol group compared with those in the control group. The median AUC for heart rate during the first 96 hours was -28/min (IQR, -37 to -21) for the esmolol group vs -6/min (95% CI, -14 to 0) for the control group with a mean reduction of 18/min (P < .001). For stroke volume index, the median AUC for esmolol was 4 mL/m(2) (IQR, -1 to 10) vs 1 mL/m2 for the control group (IQR, -3 to 5; P = .02), whereas the left ventricular stroke work index for esmolol was 3 mL/m(2) (IQR, 0 to 8) vs 1 mL/m(2) for the control group (IQR, -2 to 5; P = .03). For arterial lactatemia, median AUC for esmolol was -0.1 mmol/L (IQR, -0.6 to 0.2) vs 0.1 mmol/L for the control group (IQR, -0.3 for 0.6; P = .007); for norepinephrine, -0.11 beta g/kg/min (IQR, -0.46 to 0.02) for the esmolol group vs -0.01 beta g/kg/min (IQR, -0.2 to 0.44) for the control group (P =.003). Fluid requirements were reduced in the esmolol group: median AUC was 3975 mL/24 h (IQR, 3663 to 4200) vs 4425 mL/24 h (IQR, 4038 to 4775) for the control group (P