间羟胺对比去甲肾上腺素治疗脓毒性休克的临床研究:一项前瞻性单中心随机对照试验

Comparative study of metaraminol and norepinephrine in the treatment of septic shock: a prospective, single center, randomized, controlled trial

目的比较间羟胺与去甲肾上腺素治疗脓毒性休克的有效性和安全性。方法采用随机双盲对照研究方法,将2020年5月至2021年4月在中国科学技术大学附属第一医院重症医学科(ICU)的脓毒性休克患者随机分为间羟胺组和去甲肾上腺素组。设置开放标签的多巴胺和特利加压素,治疗目标为平均动脉压(MAP)65~75mmHg。主要疗效终点为休克纠正,次要终点包括:用药后MAP达标所需的时间;7d内开放标签血管活性药物的使用量;首次给药后第7天序贯性器官衰竭评分;ICU住院天数;总住院天数;ICU和28d死亡率;第7天内肌酐清除率。同步记录不良事件的发生情况。结果共纳入121例患者,两组患者休克纠正比例差异无统计学意义(60.00%vs.63.93%,P=0.656)。间羟胺组患者用药后MAP达标所需的时间显著长于去甲肾上腺素组[30(15,60)vs.60(30,120),P<0.001]。其他次要疗效终点两组间差异均无统计学意义。间羟胺组患者的不良事件总体发生率11.67%(7次)显著低于去甲肾上腺素组的27.87%(17次)(P=0.025)。第3、5、7天时去甲肾上腺素组患者的肌酐清除率显著低于间羟胺组(均P<0.05)。结论间羟胺治疗脓毒性休克的有效性与去甲肾上腺素相当,其安全性优于去甲肾上腺素。

Objective To compare the efficacy and safety of metaraminol and norepinephrine in the treatment of septic shock.Methods A randomized double-blind controlled trial was performed in the First Affiliated Hospital of USTC from May 2020 to April 2021.Patients with septic shock in the intensive care units(ICU)were randomly divided into metaraminol group and norepinephrine group.Open label dopamine and terlipressin were set,and the treatment target was 65~75 mmHg of mean arterial pressure(MAP).The primary efficacy end point was correcting rate of shock,and the secondary end points included the time required for MAP to reach the target after administration;use of open label vasoactive drug within 7 days;sequential organ failure score on the 7 th day after administration;length of stay in ICU;Total length of stay;ICU and 28-day mortality;endogenous creatinine clearance on day 7.The occurrence of adverse events was recorded simultaneously.Results A total of 121 patients were included(60.00%vs.63.93%,P=0.656).There was no significant difference in the correcting rate of shock between the two groups.The time required for MAP to reach the target in metaraminol group was significantly longer than that in norepinephrine group[30(15,60)vs.60(30,120),P<0.001].There was no significant difference in other secondary efficacy endpoints between the two groups.The overall incidence of adverse events in metaraminol group was 11.67%(7 times),which was significantly lower than that in norepinephrine group(27.87%,17 times)(P=0.025).On days 3,5 and 7,the creatinine clearance rate in the norepinephrine group was significantly lower than that in the metaraminol group(all P<0.05).Conclusions Metaraminol is as effective as norepinephrine in the treatment of septic shock,while its safety is better than norepinephrine.