ICM:利用生命体征轨迹构建和验证脓毒症新亚型

Abstract

Purpose: Sepsis is a heterogeneous syndrome and identification of sub-phenotypes is essential. This study used trajectories of vital signs to develop and validate sub-phenotypes and investigated the interaction of sub-phenotypes with treatment using randomized controlled trial data.脓毒症是一种异质性综合征，识别亚表型至关重要。本研究利用生命体征轨迹发展和验证亚表型，并利用随机对照试验数据探讨亚表型与治疗的相互作用。

Methods: All patients with suspected infection admitted to four academic hospitals in Emory Healthcare between 2014-2017 (training cohort) and 2018-2019 (validation cohort) were included. Group-based trajectory modeling was applied to vital signs from the first 8 h of hospitalization to develop and validate vitals trajectory sub-phenotypes. The associations between sub-phenotypes and outcomes were evaluated in patients with sepsis. The interaction between sub-phenotype and treatment with balanced crystalloids versus saline was tested in a secondary analysis of SMART (Isotonic Solutions and Major Adverse Renal Events Trial).研究纳入2014至2017年间埃默里医疗中心四家学术医院的疑似感染患者作为训练队列（n = 12,473），2018至2019年间患者作为验证队列（n = 8,256）。采用基于群体的轨迹建模方法，对患者入院前8小时的生命体征数据进行分析，以识别并验证生命体征轨迹相关的亚表型。在确诊脓毒症的患者中，评估各亚表型与临床结局之间的关联。此外，通过对SMART试验数据进行二次分析，检验不同亚表型在平衡晶体液与生理盐水治疗反应上的差异。

Results: There were 12,473 patients with suspected infection in training and 8256 patients in validation cohorts, and 4 vitals trajectory sub-phenotypes were found. Group A (N = 3483, 28%) were hyperthermic, tachycardic, tachypneic, and hypotensive. Group B (N = 1578, 13%) were hyperthermic, tachycardic, tachypneic (not as pronounced as Group A) and hypertensive. Groups C (N = 4044, 32%) and D (N = 3368, 27%) had lower temperatures, heart rates, and respiratory rates, with Group C normotensive and Group D hypotensive. In the 6,919 patients with sepsis, Groups A and B were younger while Groups C and D were older. Group A had the lowest prevalence of congestive heart failure, hypertension, diabetes mellitus, and chronic kidney disease, while Group B had the highest prevalence. Groups A and D had the highest vasopressor use (p < 0.001 for all analyses above). In logistic regression, 30-day mortality was significantly higher in Groups A and D (p < 0.001 and p = 0.03, respectively). In the SMART trial, sub-phenotype significantly modified treatment effect (p = 0.03). Group D had significantly lower odds of mortality with balanced crystalloids compared to saline (odds ratio (OR) 0.39, 95% confidence interval (CI) 0.23-0.67, p < 0.001).我们分析识别出四种生命体征轨迹亚表型： A型（n = 3,483, 28%）：表现为高热、心动过速、呼吸急促及低血压；B型（n = 1,578, 13%）：呈现高热、心动过速及呼吸急促，程度较A型轻，但伴有高血压；C型（n = 4,044, 32%）和D型（n = 3,368, 27%）：体温、心率和呼吸频率均较低，其中C型血压正常，D型伴有低血压。在6,919例脓毒症患者中，A型和B型患者年龄较轻，C型和D型年龄较大。A型患者中充血性心力衰竭、高血压、糖尿病和慢性肾病的患病率最低，而B型患者中上述合并症最为常见。A型和D型患者血管加压药使用率最高（所有分析p < 0.001）。逻辑回归分析显示，A型和D型患者的30天死亡率显著较高（p < 0.001，p = 0.03）。在SMART试验的二次分析中，不同亚表型对治疗效果存在显著影响（p = 0.03）。具体而言，D型患者在平衡晶体液组的死亡率显著低于生理盐水组（OR = 0.39，95% CI 0.23–0.67，p < 0.001）。

Conclusion: Sepsis sub-phenotypes based on vital sign trajectory were consistent across cohorts, had distinct outcomes, and different responses to treatment with balanced crystalloids versus saline. 基于生命体征轨迹的脓毒症亚表型在不同队列中具有一致性，且与不同的临床结局相关。此外，不同亚表型对平衡晶体液与生理盐水的治疗反应存在显著差异，提示亚表型可能为个体化治疗提供重要依据。