Bulle Esther B, Peake Sandra L, Finnis Mark, Bellomo Rinaldo, Delaney Anthony
Department of Intensive Care, Amsterdam University Medical Centre, Amsterdam, The Netherlands.
Department of Intensive Care Medicine, The Queen Elizabeth Hospital, Adelaide, South Australia, Australia.
Emerg Med Australas. 2021 Jun;33(3):409-417. doi: 10.1111/1742-6723.13634. Epub 2020 Oct 9.
Intravenous antimicrobial therapy within 1 h of the diagnosis of septic shock is recommended in international sepsis guidelines. We aimed to evaluate the association between antimicrobial timing and mortality in patients presenting to the ED with septic shock.
Post-hoc analysis of 1587 adult participants enrolled in the Australasian Resuscitation in Sepsis Evaluation (ARISE) multicentre trial of early goal-directed therapy for whom the time of initial antimicrobial therapy was recorded. We compared participants who had initiation of antimicrobials within the first hour (early) or later (delayed) of ED presentation. A propensity score model using inverse probability of treatment weighting was constructed to account for confounding baseline covariates. The primary outcome was 90-day mortality.
The median (interquartile range) time to initiating antimicrobials was 69 (39-112) min with 712 (44.9%) participants receiving the first dose within the first hour of ED presentation. Compared with delayed therapy, early administration was associated with increased baseline illness severity score and greater intensity of resuscitation pre-randomisation (fluid volumes, vasopressors, invasive ventilation). All-cause 90-day mortality was also higher; 22.6% versus 15.5%; unadjusted odds ratio (OR) 1.58 (95% confidence interval [CI] 1.16-2.15), P = 0.004. After inverse probability of treatment weighting, the mortality difference was non-significant; OR 1.30 (95% CI 0.95-1.76), P = 0.1. Live discharge rates from ICU (OR 0.81, 95% CI 0.72-0.91; P = 0.80) and hospital (OR 0.93, 95% CI 0.82-1.06; P = 0.29) were also not different between groups.
In this post-hoc analysis of the ARISE trial, early antimicrobial therapy was associated with increased illness severity, but 90-day adjusted mortality was not reduced.
国际脓毒症指南推荐在诊断脓毒性休克后1小时内进行静脉抗菌治疗。我们旨在评估脓毒性休克患者到急诊科就诊时抗菌治疗时机与死亡率之间的关联。
对参与澳大利亚脓毒症复苏评估（ARISE）多中心早期目标导向治疗试验的1587名成年参与者进行事后分析，记录了他们初始抗菌治疗的时间。我们比较了在急诊科就诊后第一小时内（早期）或之后（延迟）开始使用抗菌药物的参与者。构建了一个使用治疗权重逆概率的倾向评分模型，以解释混杂的基线协变量。主要结局是90天死亡率。
开始使用抗菌药物的中位（四分位间距）时间为69（39 - 112）分钟，712名（44.9%）参与者在急诊科就诊后第一小时内接受了首剂药物。与延迟治疗相比，早期给药与基线疾病严重程度评分增加以及随机分组前复苏强度更大（液体量、血管活性药物、有创通气）相关。全因90天死亡率也更高；分别为22.6%和15.5%；未调整的比值比（OR）为1.58（95%置信区间[CI] 1.16 - 2.15），P = 0.004。在进行治疗权重逆概率分析后，死亡率差异无统计学意义；OR为1.30（95% CI 0.95 - 1.76），P = 0.1。两组之间重症监护病房（ICU）的存活出院率（OR 0.81，95% CI 0.72 - 0.91；P = 0.80）和医院存活出院率（OR 0.93，95% CI 0.82 - 1.06；P = 0.29）也无差异。
在ARISE试验的这项事后分析中，早期抗菌治疗与疾病严重程度增加相关，但调整后的90天死亡率并未降低。
