Integrated Research and Treatment Center - Center for Sepsis Control and Care (CSCC), Jena University Hospital, Am Klinikum 1, 07747, Jena, Germany.
Department of Anaesthesiology and Intensive Care Medicine, Jena University Hospital, Am Klinikum 1, 07747, Jena, Germany.
Crit Care. 2022 Feb 28;26(1):51. doi: 10.1186/s13054-022-03901-9.
Timely antimicrobial treatment and source control are strongly recommended by sepsis guidelines, however, their impact on clinical outcomes is uncertain.
We performed a planned secondary analysis of a cluster-randomized trial conducted from July 2011 to May 2015 including forty German hospitals. All adult patients with sepsis treated in the participating ICUs were included. Primary exposures were timing of antimicrobial therapy and delay of surgical source control during the first 48 h after sepsis onset. Primary endpoint was 28-day mortality. Mixed models were used to investigate the effects of timing while adjusting for confounders. The linearity of the effect was investigated by fractional polynomials and by categorizing of timing.
Analyses were based on 4792 patients receiving antimicrobial treatment and 1595 patients undergoing surgical source control. Fractional polynomial analysis identified a linear effect of timing of antimicrobials on 28-day mortality, which increased by 0.42% per hour delay (OR with 95% CI 1.019 [1.01, 1.028], p ≤ 0.001). This effect was significant in patients with and without shock (OR = 1.018 [1.008, 1.029] and 1.026 [1.01, 1.043], respectively). Using a categorized timing variable, there were no significant differences comparing treatment within 1 h versus 1-3 h, or 1 h versus 3-6 h. Delays of more than 6 h significantly increased mortality (OR = 1.41 [1.17, 1.69]). Delay in antimicrobials also increased risk of progression from severe sepsis to septic shock (OR per hour: 1.051 [1.022, 1.081], p ≤ 0.001). Time to surgical source control was significantly associated with decreased odds of successful source control (OR = 0.982 [0.971, 0.994], p = 0.003) and increased odds of death (OR = 1.011 [1.001, 1.021]; p = 0.03) in unadjusted analysis, but not when adjusted for confounders (OR = 0.991 [0.978, 1.005] and OR = 1.008 [0.997, 1.02], respectively). Only, among patients with septic shock delay of source control was significantly related to risk-of death (adjusted OR = 1.013 [1.001, 1.026], p = 0.04).
Our findings suggest that management of sepsis is time critical both for antimicrobial therapy and source control. Also patients, who are not yet in septic shock, profit from early anti-infective treatment since it can prevent further deterioration. Trial registration ClinicalTrials.gov ( NCT01187134 ). Registered 23 August 2010, NCT01187134.
脓毒症指南强烈推荐及时进行抗菌治疗和源头控制，但它们对临床结局的影响尚不确定。
我们对 2011 年 7 月至 2015 年 5 月期间进行的一项包括 40 家德国医院的集群随机试验进行了计划中的二次分析。所有在参与 ICU 中接受脓毒症治疗的成年患者均被纳入。主要暴露因素是抗菌治疗的时机和脓毒症发病后 48 小时内手术源头控制的延迟。主要终点是 28 天死亡率。混合模型用于在调整混杂因素的情况下研究时机的影响。通过分数多项式和分类来研究时间的线性效应。
分析基于 4792 名接受抗菌治疗的患者和 1595 名接受手术源头控制的患者。分数多项式分析确定了抗菌治疗时机与 28 天死亡率之间的线性关系，每小时延迟增加 0.42%（OR 为 1.019 [1.01，1.028]，p≤0.001）。在有和没有休克的患者中，这种效果是显著的（OR=1.018 [1.008，1.029]和 1.026 [1.01，1.043]）。使用分类时间变量，与 1 小时内治疗相比，1-3 小时或 1 小时内治疗与 3-6 小时内治疗之间没有显著差异。超过 6 小时的延迟会显著增加死亡率（OR=1.41 [1.17，1.69]）。抗菌治疗的延迟也会增加从严重脓毒症进展为脓毒性休克的风险（每小时 OR：1.051 [1.022，1.081]，p≤0.001）。手术源头控制的时间与成功控制源头的几率降低（OR=0.982 [0.971，0.994]，p=0.003）和死亡几率增加（OR=1.011 [1.001，1.021]；p=0.03）相关，在未调整分析中，但在调整混杂因素后不相关（OR=0.991 [0.978，1.005]和 OR=1.008 [0.997，1.02]）。只有在脓毒性休克患者中，源头控制的延迟与死亡风险显著相关（调整后的 OR=1.013 [1.001，1.026]，p=0.04）。
我们的研究结果表明，脓毒症的管理在抗菌治疗和源头控制方面都具有时间紧迫性。此外，尚未发生脓毒性休克的患者也可以从早期抗感染治疗中获益，因为它可以防止病情进一步恶化。试验注册ClinicalTrials.gov（NCT01187134）。2010 年 8 月 23 日注册，NCT01187134。
