Wang Shupeng, Li Min, Duan Jun, Yi Li, Huang Xu, Chen Desheng, Li Gang
Department of Critical Care Medicine, China-Japan Friendship Hospital, Beijing 100029, China. Corresponding author: Li Gang, Email:
Zhonghua Wei Zhong Bing Ji Jiu Yi Xue. 2017 May;29(5):390-395. doi: 10.3760/cma.j.issn.2095-4352.2017.05.002.
To evaluate the effect of heart rate control with esmolol on hemodynamics, inflammatory cytokines and clinical outcomes in patients with septic shock.
A prospective randomized controlled trial was conducted. The patients with septic shock admitted to Department of Critical Care Medicine of China-Japan Friendship Hospital from August 2014 to October 2016 were enrolled. After 24 hours of resuscitation and other therapy, they were randomly divided into two groups by sealed envelope. The patients in experimental group was treated with continuous intravenous esmolol infusion for 24 hours, initial dose was 0.05 mg×kg×h, and was titrated to decrease the heart rate by 20% as compared with the value at the time of enrollment or below 95 bpm, while isotonic saline was given to control group through intravenous line at 3 mL/h for 24 hours. The differences in hemodynamic parameters at 0, 1, 4, 8, 12, 24 and 48 hours, as well as serum inflammatory cytokines and blood lactate (Lac) at 0, 12, and 24 hours, 28-day mortality were compared between the two groups.
Seventy-six septic shock patients were admitted during the study, 12 were excluded for suspicious acute myocardial infraction (AMI) or acute left heart failure or for the history of chronic obstructive pulmonary disease (COPD), 4 were quitted the study for being unable to tolerate the lowest dose of esmolol, giving up treatment, or death within 24 hours. Finally, 60 patients completed the study, 30 patients in experimental group, and 30 in control group. There were no differences in gender, age, acute physiology and chronic health evaluation II (APACHE II) score and infection source between two groups, indicating the general data between the two groups were balanced and comparable. The decrease in heart rate was more markedly in experimental group than that of control group at 1, 4, 48 hours after esmolol administration (bpm: 97.4±16.5 vs. 110.9±19.6, 95.2±15.3 vs. 105.1±17.9, 86.4±12.1 vs. 97.2±22.6, all P < 0.05), cardiac index (CI) at 8, 24, 48 hours was significantly increased (mL×s×m: 57.2±13.5 vs. 46.5±11.0, 57.7±15.7 vs. 48.7±14.7, 61.2±16.5 vs. 51.5±14.7, all P < 0.05), and stroke volume index (SVI) at 4, 8, 24 hours was significantly increased (mL/m: 34.1±6.9 vs. 29.0±8.7, 35.0±6.1 vs. 28.8±9.6, 38.3±10.1 vs. 31.9±13.2, all P < 0.05). Interleukin-1β (IL-1β) at 24 hours in experimental group was significantly higher than that of control group (ng/L: 0.15±0.06 vs. 0.13±0.05, P < 0.01). There were no differences in mean arterial pressure (MAP), Lac, white blood cell (WBC), IL-6, IL-10, and tumor necrosis factor-α (TNF-α) between the two groups, and no difference in 28-day mortality between experimental group and control group was found (30.0% vs. 36.7%,χ = 0.300, P = 0.583).
It is efficient and safe to use esmolol for heart rate control in patients with septic shock after resuscitation. Esmolol can improve cardiac performance without affecting blood pressure and Lac, but has no effect on inflammatory cytokines and prognosis.
评估艾司洛尔控制心率对感染性休克患者血流动力学、炎性细胞因子及临床结局的影响。
进行一项前瞻性随机对照试验。纳入2014年8月至2016年10月在中国-日本友好医院重症医学科收治的感染性休克患者。经过24小时复苏及其他治疗后,通过密封信封将其随机分为两组。试验组患者接受艾司洛尔持续静脉输注24小时,初始剂量为0.05mg×kg×h,并进行滴定,使心率较入组时降低20%或降至95次/分钟以下,而对照组通过静脉通路以3mL/h的速度输注等渗盐水24小时。比较两组在0、1、4、8、12、24和48小时的血流动力学参数差异,以及在0、12和24小时的血清炎性细胞因子和血乳酸(Lac)水平差异,还有28天死亡率。
研究期间共收治76例感染性休克患者,12例因可疑急性心肌梗死(AMI)或急性左心衰竭或有慢性阻塞性肺疾病(COPD)病史而被排除,4例因无法耐受艾司洛尔最低剂量、放弃治疗或在24小时内死亡而退出研究。最终,60例患者完成研究,试验组30例,对照组30例。两组在性别、年龄、急性生理与慢性健康状况评分系统II(APACHE II)评分及感染源方面无差异,表明两组的一般资料均衡且具有可比性。在给予艾司洛尔后1、4、48小时,试验组心率下降比对照组更明显(次/分钟:97.4±16.5对110.9±19.6,95.2±15.3对105.1±17.9,86.4±12.1对97.2±22.6,均P<0.05),8、24、48小时的心指数(CI)显著升高(mL×s×m:57.2±13.5对46.5±11.0,57.7±15.7对48.7±14.7,61.2±16.5对51.5±14.7,均P<0.05),4、8、24小时的每搏量指数(SVI)显著升高(mL/m:34.1±6.9对29.0±8.7,35.0±6.1对28.8±9.6,38.3±10.1对31.9±13.2,均P<0.05)。试验组24小时的白细胞介素-1β(IL-1β)显著高于对照组(ng/L:0.15±0.06对0.13±0.05,P<0.01)。两组间平均动脉压(MAP)、Lac、白细胞(WBC)、IL-6、IL-10及肿瘤坏死因子-α(TNF-α)无差异,试验组与对照组的28天死亡率也无差异(30.0%对36.7%,χ² = 0.300,P = 0.583)。
复苏后感染性休克患者使用艾司洛尔控制心率有效且安全。艾司洛尔可改善心脏功能,而不影响血压和Lac,但对炎性细胞因子及预后无影响。