Xinqiang Liu, Weiping Huang, Miaoyun Wen, Wenxin Zeng, Wenqiang Jiang, Shenglong Chen, Juhao Zeng, Hongki Zeng
Zhonghua Wei Zhong Bing Ji Jiu Yi Xue. 2015 Sep;27(9):759-63.
To investigate whether esmolol could improve clinical outcome and tissue oxygen metabolism by controlling heart rate (HR) in patients with septic shock.
A single-center double-blinded randomized controlled trial was conducted. The patients suffering from septic shock received 6-hour early goal directed herapy (EGDT) with pulmonary artery wedge pressure ≥ 12 mmHg (1 mmHg = 0.133 kPa) or central venous pressure CVP) ≥ 12 mmHg requiring norepinephrine to maintain mean arterial pressure (MAP) ≥ 65 mmHg and HR ≥ 95 bpm admitted to intensive care unit (ICU) of Guangdong General Hospital from September 2013 to September 2014 were enrolled. They were randomly divided into esmolol group and control group by computer-based random number generator. All patients received conventional basic treatment, while those in the esmolol group received in addition persistent esmolol infusion by micro pump with dosage of 0.05 mg · kg(-1) · min(-1) with the dosage adjusted to maintain HR lower than 100 bpm within 24 hours. The patients in control group did not receive drug intervention for HR. The primary end-points consisted of length of stay in ICU and 28-day mortality. The secondary end-points included hemodynamic parameters [HR, MAP, CVP, cardiac index (CI), stroke volume index (SVI), systemic vascular resistance index (SVRI)] and tissue oxygen metabolism parameters [central venous oxygen saturation (ScvO2), lactate level (Lac)] before and 24, 48, 72 hours after the treatment.
A total of 48 patients with septic shock were enrolled with 24 patients in esmolol group and 24 in control group. (1) The primary end-points: compared with control group, the length of stay in the ICU in the esmolol group was significantly shortened (days: 13.75 ± 8.68 vs. 21.70 ± 6.06, t = 3.680, P = 0.001), and 28-day mortality was significantly lowered [25.0% (6/24) vs. 62.5% (15/24 ), χ2 = 6.857, P = 0.009]. (2) The secondary end-points: there were no significant difference in the hemodynamic and tissue metabolism parameters before treatment between two groups. No significant difference was found between before and after treatment of all above parameters in control group. HR and Lac in the esmolol group were obviously declined, SVI, SVRI, SCvO2 were gradually increased, but no significant difference in MAP, CVP, and CI was found. Compared with the control group, HR in the esomolol group was significantly lowered (bpm: 84.4 ± 3.5 vs. 111.2 ± 7.2, P < 0.01), SVRI and ScvO2 were significantly increased from 24 hours [SVRI (kPa · s · L(-1) ·m(-2)): 137.9 ± 1.6 vs. 126.9 ± 1.3, ScvO2: 0.652 ± 0.017 vs. 0.620 ± 0.017, both P < 0.01]; SVI was significantly increased (mL/m2: 39.9 ± 2.2 vs. 36.8 ± 1.7, P < 0.01) and Lac level significantly declined from 48 hours (mmol/L: 2.8 ± 0.3 vs. 3.4 ± 0.3, P < 0.01).
The results demonstrate that HR controlled by a titrated esmolol infusion given to septic shock patients was associated with an improvement in tissue metabolism, reduction in the length of ICU stay and lowering of 28-day mortality.
探讨艾司洛尔能否通过控制脓毒性休克患者的心率（HR）来改善临床结局和组织氧代谢。
进行一项单中心双盲随机对照试验。选取2013年9月至2014年9月入住广东省人民医院重症监护病房（ICU）、患有脓毒性休克且接受6小时早期目标导向治疗（EGDT）、肺动脉楔压≥12 mmHg（1 mmHg = 0.133 kPa）或中心静脉压（CVP）≥12 mmHg、需要去甲肾上腺素维持平均动脉压（MAP）≥65 mmHg且HR≥95次/分钟的患者。通过计算机随机数字生成器将他们随机分为艾司洛尔组和对照组。所有患者均接受常规基础治疗，而艾司洛尔组患者还通过微量泵持续输注艾司洛尔，剂量为0.05 mg·kg⁻¹·min⁻¹，并调整剂量以在24小时内将HR维持在低于100次/分钟。对照组患者未接受针对HR的药物干预。主要终点包括ICU住院时间和28天死亡率。次要终点包括治疗前及治疗后24、48、72小时的血流动力学参数[HR、MAP、CVP、心脏指数（CI）、每搏量指数（SVI）、全身血管阻力指数（SVRI）]和组织氧代谢参数[中心静脉血氧饱和度（ScvO₂）、乳酸水平（Lac）]。
共纳入48例脓毒性休克患者，艾司洛尔组24例，对照组24例。（1）主要终点：与对照组相比，艾司洛尔组的ICU住院时间显著缩短（天数：13.75±8.68 vs. 21.70±6.06，t = 3.680，P = 0.001），28天死亡率显著降低[25.0%（6/24）vs. 62.5%（15/24），χ² = 6.857，P = 0.009]。（2）次要终点：两组治疗前的血流动力学和组织代谢参数无显著差异。对照组上述所有参数治疗前后无显著差异。艾司洛尔组的HR和Lac明显下降，SVI、SVRI、ScvO₂逐渐升高，但MAP、CVP和CI无显著差异。与对照组相比，艾司洛尔组的HR显著降低（次/分钟：84.4±3.5 vs. 111.2±7.2，P < 0.01），从24小时起SVRI和ScvO₂显著升高[SVRI（kPa·s·L⁻¹·m⁻²）：137.9±1.6 vs. 126.9±1.
