ICM:1小时集束化治疗方案对急诊疑似脓毒症患者死亡率影响:一项阶梯楔形随机临床试验

Abstract

Purpose: The efficacy of the 1‐h bundle for emergency department (ED) patients with suspected sepsis, which includes lactate measurement, blood culture, broad‐spectrum antibiotics administration, administration of 30 mL/kg crystalloid fluid for hypotension or lactate ≥ 4 mmol/L, remains controversial.

目的：评估急诊科(ED)疑似脓毒症患者的1小时集束化治疗方案的效果，该方案包括乳酸测量、血培养、广谱抗生素管理以及对低血压或乳酸≥4 mmol/L的患者进行30 mL/kg晶体液复苏。

Methods: We carried out a pragmatic stepped‐wedge cluster‐randomized trial in 23 EDs in France and Spain. Adult patients with Sepsis‐3 criteria or a quick sequential organ failure assessment (SOFA) score ≥ 2 or a lactate > 2 mmol/L were eligible. The intervention was the implementation of the 1‐h sepsis bundle. The primary outcome was in‐hos‐ pital mortality truncated at 28 days. Secondary outcomes included volume of fluid resuscitation at 24 h, acute heart failure at 24 h, SOFA score at 72 h, intensive care unit (ICU) length of stay, number of days on mechanical ventilation or renal replacement therapy, vasopressor free days, unnecessary antibiotic administration, and mortality at 28 days. 1148 patients were planned to be analysed; the study period ended after 873 patients were included.

方法：在法国和西班牙的23个急诊科进行了一项阶梯式楔形群组随机试验。纳入符合Sepsis-3标准或快速序贯器官衰竭评分(SOFA)≥2或乳酸>2 mmol/L的成年患者。干预措施为实施1小时脓毒症集束化治疗。主要结果是28天内的住院死亡率。次要结果包括24小时内的液体复苏量、24小时内急性心力衰竭发生率、72小时SOFA评分、ICU住院时间、28天内机械通气或肾脏替代治疗天数、28天内无血管活性药物天数、28天内非必要抗生素使用以及28天内全因死亡率。计划分析1148例患者，研究在纳入873例患者后结束。

Results: 872 patients (mean age 66, 42% female) were analyzed: 387 (44.4%) in the intervention group and 485 (55.6%) in the control group. Median SOFA score was 3 [1–5]. Median time to antibiotic administration was 40 min in the intervention group vs 113 min in the control group (difference − 73 [95% confidence interval (CI) − 93 to − 53]). There was a significantly higher rate, volume, and shorter time to fluid resuscitation within 3 h in the intervention group. There were 47 (12.1%) in‐hospital deaths in the intervention group compared to 61 (12.6%) in the control group (difference in percentage − 0.4 [95% CI − 5.1 to 4.2], adjusted relative risk (aRR) 0.81 [95% CI 0.48 to 1.39]). There were no differences between groups for other secondary endpoints.

结果：872例患者(平均年龄66岁，女性占比42%)被分析：387例(44.4%)在干预组，485例(55.6%)在对照组。干预组抗生素使用中位时间为40分钟，对照组为113分钟(差异-73分钟[95%置信区间(CI)-93至-53])。干预组在3小时内液体复苏率、复苏量和时间均显著高于对照组。干预组有47例(12.1%)住院死亡，对照组有61例(12.6%)(差异百分比-0.4[95%CI-5.1至4.2]，调整相对风险(aRR)0.81[95%CI 0.48至1.39])。两组在其他次要终点无差异。

Conclusions: Among patients with suspected sepsis in the ED, the implementation of the 1‐h sepsis bundle was not associated with significant difference in in‐hospital mortality. However, this study may be underpowered to report a statistically significant difference between groups.

结论：在急诊科疑似脓毒症患者中，实施1小时脓毒症集束化治疗与住院死亡率无显著差异。但需要注意是，本研究未能报告组间统计学差异可能是存在统计功效不足情况。