Brown Samuel M, Beesley Sarah J, Lanspa Michael J, Grissom Colin K, Wilson Emily L, Parikh Samir M, Sarge Todd, Talmor Daniel, Banner-Goodspeed Valerie, Novack Victor, Thompson B Taylor, Shahul Sajid
1Pulmonary and Critical Care Medicine, Intermountain Medical Center, Murray, UT USA.
2Pulmonary and Critical Care Medicine, University of Utah, Salt Lake City, UT USA.
Pilot Feasibility Stud. 2018 Aug 3;4:132. doi: 10.1186/s40814-018-0321-5. eCollection 2018.
High adrenergic tone appears to be associated with mortality in septic shock, while adrenergic antagonism may improve survival. In preparation for a randomized trial, we conducted a prospective, single-arm pilot study of esmolol infusion for patients with septic shock and tachycardia that persists after adequate volume expansion.
From April 2016 to March 2017, we enrolled patients admitted to an intensive care unit with sepsis who were receiving vasopressor infusion and were tachycardic despite adequate volume expansion. All patients received a continuous intravenous infusion of esmolol, targeted to heart rate 80-90/min, while receiving vasopressors. The feasibility outcomes were proportion of eligible patients consented, compliance with pre-infusion safety check, and compliance with the titration protocol. The primary clinical outcome was organ-failure-free days (OFFD) at 28 days.
We enrolled 7 of 10 eligible patients. Mean age was 46 (± 19) years, and mean admission APACHE II was 28 (± 8). Median norepinephrine infusion rate at the initiation of esmolol infusion was 0.20 (0.14-0.23) μg/kg/min. Compliance with the safety check was 100%; compliance with components of the titration protocol was 98-100%. OFFD were 26 (24.5-26); all patients survived to day 90. Median peak esmolol infusion was 50 (25-50) μg/kg/min. Median peak norepinephrine infusion rate during esmolol infusion was 0.46 (0.13-0.50) μg/kg/min. Four patients achieved target heart rate. Protocol-defined stop events, suggesting possible intolerance to a given infusion rate, occurred in three patients, all of whom were receiving at least 50 μg/kg/min of esmolol.
In a pilot, single-arm study, we report the first published experience with esmolol infusion in tachycardic patients with septic shock in the United States. These findings support a phase 2 trial of esmolol infusion for septic shock. Lower infusion rates of esmolol infusion may be better tolerated and more feasible than higher infusion rates for such a trial.
This study was retrospectively registered at ClinicalTrials.gov (NCT02841241) on 19 July 2016.
高肾上腺素能状态似乎与感染性休克患者的死亡率相关，而肾上腺素能拮抗作用可能会提高生存率。在准备一项随机试验时，我们对感染性休克且在充分扩容后仍存在心动过速的患者进行了一项前瞻性单臂试验性研究，给予艾司洛尔静脉输注。
2016年4月至2017年3月，我们纳入了入住重症监护病房、患有脓毒症、正在接受血管升压药输注且尽管充分扩容仍心动过速的患者。所有患者在接受血管升压药治疗的同时，接受艾司洛尔持续静脉输注，目标心率为80 - 90次/分钟。可行性指标包括同意参与的合格患者比例、输液前安全检查的依从性以及滴定方案的依从性。主要临床结局是28天时无器官衰竭天数（OFFD）。
我们纳入了10名合格患者中的7名。平均年龄为46（±19）岁，入院时急性生理学与慢性健康状况评分系统（APACHE II）平均为28（±8）。开始输注艾司洛尔时去甲肾上腺素的中位输注速率为0.20（0.14 - 0.23）μg/kg/分钟。安全检查的依从性为100%；滴定方案各部分的依从性为98% - 100%。OFFD为26（24.5 - 26）；所有患者均存活至90天。艾司洛尔的中位峰值输注量为50（25 - 50）μg/kg/分钟。输注艾司洛尔期间去甲肾上腺素的中位峰值输注速率为0.46（0.13 - 0.50）μg/kg/分钟。4名患者达到目标心率。3名患者发生了方案定义的停药事件，提示可能对给定的输注速率不耐受，这3名患者均接受了至少50μg/kg/分钟的艾司洛尔。
在一项单臂试验性研究中，我们报告了美国首次发表的关于在感染性休克心动过速患者中输注艾司洛尔的经验。这些发现支持进行艾司洛尔治疗感染性休克的2期试验。对于这样一项试验，较低的艾司洛尔输注速率可能比较高的输注速率耐受性更好且更可行。
本研究于2016年7月19日在ClinicalTrials.gov（NCT02841241）进行了回顾性注册。
