艾司洛尔通过控制心室率改善感染性休克患者临床预后和组织氧代谢

Esmolol improves clinical outcome and tissue oxygen metabolism in patients with septic shock through controlling heart rate

目的探讨艾司洛尔是否通过控制心室率改善感染性休克患者的临床预后和组织氧代谢。方法采用单中心随机双盲对照研究。选择2013年9月至2014年9月人住广东省人民医院重症加强治疗病房（ICU），经6h早期目标导向治疗（EGDT）后肺动脉楔压≥12mmHg（1mmHg=0．133kPa）或中心静脉压（CVP）≥12mmHg，且需要去甲肾上腺素（NE）维持平均动脉压（MAP）≥65mmHg、心率（HR）≥95次／min的感染性休克患者，按随机数字表法分为艾司洛尔组和对照组。两组患者均给予常规基础治疗，艾司洛尔组同时经上腔静脉导管用微量泵持续泵人艾司洛尔0．05mg·kg^-1·min^-1，并根据HR调整剂量，24h内控制HR〈100次／min；对照组则不对HR进行特殊干预。主要观察目标：ICU住院时间和28d病死率；次要观察目标：治疗前及治疗后24、48、72h血流动力学指标[HR、MAP、CVP、心排血指数（CI）、每搏量指数（SVI）、外周血管阻力指数（SVRI）]和组织氧代谢指标[中心静脉血氧饱和度（ScvO2）、血乳酸（Lac）]。结果共48例感染性休克患者入选，对照组和艾司洛尔组各24例。①主要观察目标：与对照组比较，艾司洛尔组ICU住院时间明显缩短（d：13．75±8．68比21．70±6．06，t=3．680，P=0．001），28d病死率明显降低[25．0％（6／24）比62．5％（15／24），x^2=6．857，P=0．009]。②次要观察目标：两组患者治疗前血流动力学指标、组织氧代谢指标比较差异均无统计学意义。对照组治疗前后各指标均无明显改变；艾司洛尔组治疗后HR明显减慢，SVI、SVRI、ScvO2逐渐升高，Lac逐渐降低，而MAP、CVP、CI无明显改变。与对照组比较，艾司洛尔组治疗后24h起HR即明显减慢（次／min：84．4±3．5比111．2±7．2，P〈0．01），SVRI和ScvO2即明显升高[SVRI（kPa·s·L-1·m-2）：137．9±1．6比126．9±1.3，ScvO2：0．652±0．017比0．620±0．017，均P〈0．01]；48h起SVI明显升高（mL／m2：39．9±2．2比36．8±1．7，P〈0．01），Lac明显降低（mmol／L：2．8±0.3比3．4±0．3，P〈0．01）。结论艾司洛尔可能通过控制感染性休克患者的HR，改善组织氧代谢，从而缩短患者ICU住院时间，降低28d病死率。

Objective To investigate whether esmolol could improve clinical outcome and tissue oxygen metabolism by controlling heart rate （HR） in patients with septic shock. Methods A single-center double-blinded randomized controlled trial was conducted. The patients suffering from septic shock received 6-hour early goal directed therapy （EGDT） with pulmonary artery wedge pressure I〉 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. Results 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 ）, X2 = 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/mZ： 39.9 ± 2.2 vs. 36.8 ± 1.7, P 〈 0.01 ） and Lae level significantly declined from 48 hours （mmol/L： 2.8 ± 0.3 vs. 3.4 ± 0.3, P 〈 0.01 ）. Conclusion 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.