Abstract: Objective To explore the safety and efficacy of propranolol,an adrenergic receptor inhibitor,in the treatment of severe traumatic brain injury(TBI) patients. Methods This study is a phase II,single center,double-blind,randomized controlled trial that enrolled patients with severe TBI(intracranial hemorrhage and Glasgow Coma Scale ≤8) within 24 hours of admission to our ICU from March 2022 to January 2024.The patient was randomly treated with propranolol or placebo for 7 days.The primary outcome was ventilator free days(VFDs) at 28 days.Secondary outcomes included catecholamine levels,ICU length of stay,and in-hospital mortality. Results There were no significant differences in gender distribution,age,Injury Severity Score(ISS),Sequential Organ Failure Assessment(SOFA),and Marshall CT grading distribution between the two groups,indicating comparability of baseline data.There was no significant difference in the average number of days without ventilators(VFD) between the treatment group and the placebo group(treatment group:14.2±5.3 days vs.placebo group:14.5±5.6 days)(t=0.277,P=0.783).In addition,there were no statistically significant differences in secondary outcomes such as plasma catecholamine levels,ICU length of stay(treatment group:20.5±7.3 days vs.placebo group:20.9±7.9 days)(t=0.264,P=0.792),and in-hospital mortality rate(treatment group:15.7% vs.placebo group:24.0%)(χ²=1.099,P=0.295) between the two groups before and after treatment.The median survival time in the placebo group was 309 days,while the median survival time in the propranolol group was not achieved.There was significant difference in survival rate between the two groups(HR=0.453,P=0.043).During the treatment period,neither group experienced any cardiac complications or other serious adverse events.One patient in the treatment group developed temporary bradycardia,which did not require intervention and continued drug use.No patient withdrew from the study due to adverse reactions. Conclusion The use of propranolol for adrenergic blockade treatment of severe traumatic brain injury is safe and feasible,and brought significant survival benefits to patients.

Key words: Adrenergic receptor inhibitors, Propranolol, Brain injury, ICU

摘要： 目的 探索肾上腺素能受体抑制剂普萘洛尔治疗严重创伤性脑损伤(severe traumatic brain injury,TBI)患者的安全性和有效性。方法 该研究为II期、单中心、双盲、随机对照试验,纳入患者为2022年3月至2024年1月在我院ICU入院24小时内患有严重TBI(颅内出血和格拉斯哥昏迷评分≤8)的患者。患者随机接受普萘洛尔或安慰剂治疗7天。主要结局是28天时无呼吸机天数(ventilator-free days,VFDs)。次要结局包括儿茶酚胺水平、ICU住院时间、住院死亡率。结果 两组之间性别分布,年龄,损伤严重度评分(injury severity score,ISS),序贯器官衰竭估计评分(sequential organ failure assessment SOFA)、马歇尔CT分级分布之间均无明显差异,基线资料具有可比性。治疗组和安慰剂组的平均无呼吸机天数(VFD)没有差异(治疗组:14.2±5.3 天vs.安慰剂组:14.5±5.6天)(t=0.277,P=0.783)。此外,两组患者治疗前后血浆儿茶酚胺水平、ICU住院时间(治疗组:20.5±7.3天vs.安慰剂组:20.9±7.9天)(t=0.264,P=0.792)和住院死亡率(治疗组:15.7%vs.安慰剂组:24.0%)(卡方值=1.099,P=0.295)等次要结局差异均无统计学意义。安慰剂组中位生存天数为309天,普萘洛尔组中位生存未达到,两组的生存率存在显著差异(HR=0.453,P=0.043)。两组患者在治疗期间均未出现心脏并发症及其他严重不良事件,治疗组中有1名患者出现暂时性缓慢心律失常,不需要干预,继续药物使用,无患者因不良反应退出研究。结论 使用普萘洛尔进行肾上腺素能阻滞治疗严重创伤性脑损伤后是安全可行的,可以给患者带来生存获益。

关键词: 肾上腺素能受体抑制剂, 普萘洛尔, 颅脑损伤, ICU