Risk of Misleading Conclusions in Observational Studies of Time-to-Antibiotics and Mortality in Suspected Sepsis.
Risk of Misleading Conclusions in Observational Studies of Time-to-Antibiotics and Mortality in Suspected Sepsis.
复制标题
疑似脓毒症患者使用抗生素时间和死亡率的观察性研究中存在误导性结论的风险。
DOI：
10.1093/cid/ciad450
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发表时间：
2023
期刊：
影响因子：
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通讯作者：
Klompas,Michael
中科院分区：
文献类型：
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作者：
Pak,TheodoreR;Young,Jessica;McKenna,CarolineS;Agan,Anna;DelloStritto,Laura;Filbin,MichaelR;Dutta,Sayon;Kadri,SameerS;Septimus,EdwardJ;Rhee,Chanu;Klompas,Michael
有影响力的研究得出结论，每隔一小时使用抗生素就会增加败血症的死亡率。然而，这些分析经常(1)对有限的协变量进行调整，(2)包括延迟使用抗生素的患者，(3)合并败血症和感染性休克，以及(4)使用线性模型假设每小时延迟具有相同的影响。我们评估了这些分析选择对使用抗生素时间与死亡率之间关系的影响。方法回顾性分析2015-2022年在5家医院收治的疑似感染（血培养及到达后≤24 h静脉注射抗生素）的成人104 248例，其中疑似感染性休克25 990例，无休克的23 619例。我们使用多变量回归来计算在更广泛的混杂调整、更短的最大抗生素时间间隔、疾病严重程度分层和去除线性小时关联的假设下，使用抗生素时间与住院死亡率之间的关联。改变协变量、最大使用抗生素时间和严重程度分层改变了观察到的使用抗生素时间与死亡率之间相关性的大小、方向和意义。在治疗≤6小时的完全校正模型中，每小时与脓毒性休克的死亡率较高相关（校正优势比[aOR]: 1.07; 95% CI: 1.04-1.11），但与无休克的脓毒症（aOR: 1.03; 0.98 - 1.09）或单纯怀疑感染（aOR: 0.99; 0.94 - 1.05）无关。每小时单独建模证实每小时延迟与脓毒症休克死亡率增加相关，但只有延迟bb60小时与脓毒症无休克死亡率增加相关。结论败血症患者使用抗生素时间与死亡率之间的关系对分析选择高度敏感。如果不能充分解决这些问题，可能会得出误导性的结论。
BackgroundInfluential studies conclude that each hour until antibiotics increases mortality in sepsis. However, these analyses often (1) adjusted for limited covariates, (2) included patients with long delays until antibiotics, (3) combined sepsis and septic shock, and (4) used linear models presuming each hour delay has equal impact. We evaluated the effect of these analytic choices on associations between time-to-antibiotics and mortality.MethodsWe retrospectively identified 104 248 adults admitted to 5 hospitals from 2015–2022 with suspected infection (blood culture collection and intravenous antibiotics ≤24 h of arrival), including 25 990 with suspected septic shock and 23 619 with sepsis without shock. We used multivariable regression to calculate associations between time-to-antibiotics and in-hospital mortality under successively broader confounding-adjustment, shorter maximum time-to-antibiotic intervals, stratification by illness severity, and removing assumptions of linear hourly associations.ResultsChanging covariates, maximum time-to-antibiotics, and severity stratification altered the magnitude, direction, and significance of observed associations between time-to-antibiotics and mortality. In a fully adjusted model of patients treated ≤6 hours, each hour was associated with higher mortality for septic shock (adjusted odds ratio [aOR]: 1.07; 95% CI: 1.04–1.11) but not sepsis without shock (aOR: 1.03; .98–1.09) or suspected infection alone (aOR: .99; .94–1.05). Modeling each hour separately confirmed that every hour of delay was associated with increased mortality for septic shock, but only delays >6 hours were associated with higher mortality for sepsis without shock.ConclusionsAssociations between time-to-antibiotics and mortality in sepsis are highly sensitive to analytic choices. Failure to adequately address these issues can generate misleading conclusions.