The procalcitonin trajectory as an effective tool for identifying sepsis patients at high risk of mortality

IF 8.8 1区 医学 Q1 CRITICAL CARE MEDICINE
Xu Wang, Shilong Lin, Ming Zhong, Jieqiong Song
{"title":"The procalcitonin trajectory as an effective tool for identifying sepsis patients at high risk of mortality","authors":"Xu Wang, Shilong Lin, Ming Zhong, Jieqiong Song","doi":"10.1186/s13054-024-05100-0","DOIUrl":null,"url":null,"abstract":"<p>Sepsis is a critical condition that significantly burdens healthcare systems globally. Given the heterogeneity among sepsis patients, identifying high-risk mortality groups is crucial [1]. Procalcitonin (PCT) is a well-established biomarker for evaluating sepsis severity and guiding antibiotic therapy [2]. In practice, PCT is usually measured repeatedly during the hospital stay. While single PCT values are helpful, dynamic trends through repeated measurements offer deeper insights into patient prognosis. Traditional analysis methods often fail to fully capture the complexity of these data [3]. By employing a hierarchical linear mixed-effects (HLME) model [4], this study aims to explore distinct PCT trajectories in sepsis patients and their association with mortality, providing a refined approach to risk stratification.</p><p>We here report our main findings in this study. The medical ethics committee of Zhongshan Hospital Fudan University reviewed and approved this study (B2021-501R). Informed consent was waived because of the retrospective nature of the study and the analysis used anonymous clinical data. Between Jan 2019 and March 2024, 537 patients (167 females, 370 males; median age 69 years old [IQR 59–77]) were included. The proportion of patients with septic shock is 47.5%. Abdomen (274/51.0%) and respiratory (202/37.6%) were the two main sites of infection. The median length of stay (LOS) was 10 days [IQR 4–20] in ICU and 15 days [IQR 10–25] in hospital. One hundred sixty-five in-hospital deaths were observed.</p><p>A total of 2492 PCT measurements were available for trajectory modeling analyses. Three classes were identified using the HLME model (Fig. 1A). Class 1, also known as the “high-value-slow-decrease” class, included 43 patients (8%) and was characterized by initially high PCT values that remained stable for the first three days before gradually declining. Class 2, the “consistent-low” class, included 354 patients (66%) and displayed low initial PCT values that remained consistently low over the first 7 days in the ICU. Class 3, the “high-value-fast-decrease” class, included 140 patients (26%) and was marked by high initial PCT values that declined rapidly over time. Baseline characteristics differed significantly between the three PCT classes (Table 1). Patients in Class 1 and Class 3 had higher baseline SOFA scores and required more norepinephrine to maintain blood pressure compared to Class 2. In-hospital mortality was highest in Class 1 (42%) compared to Class 2 (32%) and Class 3 (24%) (<i>P</i> = 0.044). Baseline variables (age, sex, baseline SOFA, baseline lactate, presence of septic shock, surgical intervention, infection sites) and PCT classes were included in the Cox proportional hazards model for in-hospital mortality. With Class 1 as the reference level, Class 2 (HR: 0.507 [95% CI 0.287–0.895], <i>P</i> = 0.020) and Class 3 (HR 0.449 [95% CI 0.244–0.827], <i>P</i> = 0.011) were independent protective factors for in-hospital mortality. Kaplan–Meier survival curves were used to illustrate the in-hospital mortality of the 3 classes (Fig. 1B).</p><figure><figcaption><b data-test=\"figure-caption-text\">Fig. 1</b></figcaption><picture><source srcset=\"//media.springernature.com/lw685/springer-static/image/art%3A10.1186%2Fs13054-024-05100-0/MediaObjects/13054_2024_5100_Fig1_HTML.png?as=webp\" type=\"image/webp\"/><img alt=\"figure 1\" aria-describedby=\"Fig1\" height=\"985\" loading=\"lazy\" src=\"//media.springernature.com/lw685/springer-static/image/art%3A10.1186%2Fs13054-024-05100-0/MediaObjects/13054_2024_5100_Fig1_HTML.png\" width=\"685\"/></picture><p><b>A</b> Shows the 3 distinct procalcitonin classes. <b>B</b> Contains Kaplan–Meier curves for patients in the 3 classes. Class 1: “high-value-slow-decrease” class; Class 2: “consistent-low” class; Class 3: “high-value-fast-decrease” class</p><span>Full size image</span><svg aria-hidden=\"true\" focusable=\"false\" height=\"16\" role=\"img\" width=\"16\"><use xlink:href=\"#icon-eds-i-chevron-right-small\" xmlns:xlink=\"http://www.w3.org/1999/xlink\"></use></svg></figure><figure><figcaption><b data-test=\"table-caption\">Table 1 Comparison of baseline characteristics among the three PCT classes</b></figcaption><span>Full size table</span><svg aria-hidden=\"true\" focusable=\"false\" height=\"16\" role=\"img\" width=\"16\"><use xlink:href=\"#icon-eds-i-chevron-right-small\" xmlns:xlink=\"http://www.w3.org/1999/xlink\"></use></svg></figure><p>Three distinct PCT trajectories were identified in this study. Despite notable baseline differences across the classes, the “high-value-slow-decrease” PCT trajectory is an independent risk factor for higher in-hospital mortality. Given the strong link between PCT trajectories and mortality, continuous monitoring of PCT levels is essential for clinicians to detect potential high-risk sepsis patients. The insights from this study provide clinicians with information to optimize clinical decision-making and may support the development of more personalized and effective sepsis management strategies, ultimately benefiting patient outcomes.</p><p>The datasets generated and/or analysed during the current study are not publicly available due to containing information that could compromise the privacy of research participants, but are available from the corresponding authors, JS and MZ, on reasonable request.</p><ol data-track-component=\"outbound reference\" data-track-context=\"references section\"><li data-counter=\"1.\"><p>Evans L, Rhodes A, Alhazzani W, Antonelli M, Coopersmith CM, French C, Machado FR, McIntyre L, Ostermann M, Prescott HC, et al. 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Hoboken: Wiley; 2001.</p><p>Google Scholar </p></li></ol><p>Download references<svg aria-hidden=\"true\" focusable=\"false\" height=\"16\" role=\"img\" width=\"16\"><use xlink:href=\"#icon-eds-i-download-medium\" xmlns:xlink=\"http://www.w3.org/1999/xlink\"></use></svg></p><p>This research received funding from Shanghai municipal hospital diagnosis and treatment technology promotion and optimization management project (SHDC22022203).</p><h3>Authors and Affiliations</h3><ol><li><p>Department of Critical Care Medicine, Zhongshan Hospital of Fudan University, No. 180, Fenglin Road, Xuhui District, Shanghai, China</p><p>Xu Wang, Shilong Lin, Ming Zhong &amp; Jieqiong Song</p></li></ol><span>Authors</span><ol><li><span>Xu Wang</span>View author publications<p>You can also search for this author in <span>PubMed<span> </span>Google Scholar</span></p></li><li><span>Shilong Lin</span>View author publications<p>You can also search for this author in <span>PubMed<span> </span>Google Scholar</span></p></li><li><span>Ming Zhong</span>View author publications<p>You can also search for this author in <span>PubMed<span> </span>Google Scholar</span></p></li><li><span>Jieqiong Song</span>View author publications<p>You can also search for this author in <span>PubMed<span> </span>Google Scholar</span></p></li></ol><h3>Contributions</h3><p>XW was responsible for the methodological design, coordination, data preparation, and statistical analysis. SL contributed to data collection and statistical analysis. XW drafted and revised the manuscript. JS and MZ conceived and designed the study and assisted in drafting the paper. XW, SL, MZ, and JS contributed to the preparation and critical review of the manuscript. All authors approved the final manuscript.</p><h3>Corresponding authors</h3><p>Correspondence to Ming Zhong or Jieqiong Song.</p><h3>Competing interests</h3>\n<p>The authors declare no competing interests.</p><h3>Publisher’s note</h3><p>Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.</p><p><b>Open Access</b> This article is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License, which permits any non-commercial use, sharing, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if you modified the licensed material. You do not have permission under this licence to share adapted material derived from this article or parts of it. 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0-.92-.08-1.33-.25-.41-.16-.77-.4-1.08-.7-.3-.31-.54-.69-.72-1.13-.17-.44-.26-.95-.26-1.52zm4.61-.62c0-.55-.11-.98-.34-1.28-.23-.31-.58-.47-1.06-.47-.41 0-.77.15-1.08.45-.31.29-.5.73-.57 1.3zm3.01 2.23c.31.24.61.43.92.57.3.13.63.2.98.2.38 0 .65-.08.83-.23s.27-.35.27-.6c0-.14-.05-.26-.13-.37-.08-.1-.2-.2-.34-.28-.14-.09-.29-.16-.47-.23l-.53-.22c-.23-.09-.46-.18-.69-.3-.23-.11-.44-.24-.62-.4s-.33-.35-.45-.55c-.12-.21-.18-.46-.18-.75 0-.61.23-1.1.68-1.49.44-.38 1.06-.57 1.83-.57.48 0 .91.08 1.29.25s.71.36.99.57l-.74.98c-.24-.17-.49-.32-.73-.42-.25-.11-.51-.16-.78-.16-.35 0-.6.07-.76.21-.17.15-.25.33-.25.54 0 .14.04.26.12.36s.18.18.31.26c.14.07.29.14.46.21l.54.19c.23.09.47.18.7.29s.44.24.64.4c.19.16.34.35.46.58.11.23.17.5.17.82 0 .3-.06.58-.17.83-.12.26-.29.48-.51.68-.23.19-.51.34-.84.45-.34.11-.72.17-1.15.17-.48 0-.95-.09-1.41-.27-.46-.19-.86-.41-1.2-.68z" fill="#535353"/></g></svg>\" width=\"57\"/><h3>Cite this article</h3><p>Wang, X., Lin, S., Zhong, M. <i>et al.</i> The procalcitonin trajectory as an effective tool for identifying sepsis patients at high risk of mortality. <i>Crit Care</i> <b>28</b>, 312 (2024). https://doi.org/10.1186/s13054-024-05100-0</p><p>Download citation<svg aria-hidden=\"true\" focusable=\"false\" height=\"16\" role=\"img\" width=\"16\"><use xlink:href=\"#icon-eds-i-download-medium\" xmlns:xlink=\"http://www.w3.org/1999/xlink\"></use></svg></p><ul data-test=\"publication-history\"><li><p>Received<span>: </span><span><time datetime=\"2024-09-11\">11 September 2024</time></span></p></li><li><p>Accepted<span>: </span><span><time datetime=\"2024-09-14\">14 September 2024</time></span></p></li><li><p>Published<span>: </span><span><time datetime=\"2024-09-19\">19 September 2024</time></span></p></li><li><p>DOI</abbr><span>: </span><span>https://doi.org/10.1186/s13054-024-05100-0</span></p></li></ul><h3>Share this article</h3><p>Anyone you share the following link with will be able to read this content:</p><button data-track=\"click\" 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Abstract

Sepsis is a critical condition that significantly burdens healthcare systems globally. Given the heterogeneity among sepsis patients, identifying high-risk mortality groups is crucial [1]. Procalcitonin (PCT) is a well-established biomarker for evaluating sepsis severity and guiding antibiotic therapy [2]. In practice, PCT is usually measured repeatedly during the hospital stay. While single PCT values are helpful, dynamic trends through repeated measurements offer deeper insights into patient prognosis. Traditional analysis methods often fail to fully capture the complexity of these data [3]. By employing a hierarchical linear mixed-effects (HLME) model [4], this study aims to explore distinct PCT trajectories in sepsis patients and their association with mortality, providing a refined approach to risk stratification.

We here report our main findings in this study. The medical ethics committee of Zhongshan Hospital Fudan University reviewed and approved this study (B2021-501R). Informed consent was waived because of the retrospective nature of the study and the analysis used anonymous clinical data. Between Jan 2019 and March 2024, 537 patients (167 females, 370 males; median age 69 years old [IQR 59–77]) were included. The proportion of patients with septic shock is 47.5%. Abdomen (274/51.0%) and respiratory (202/37.6%) were the two main sites of infection. The median length of stay (LOS) was 10 days [IQR 4–20] in ICU and 15 days [IQR 10–25] in hospital. One hundred sixty-five in-hospital deaths were observed.

A total of 2492 PCT measurements were available for trajectory modeling analyses. Three classes were identified using the HLME model (Fig. 1A). Class 1, also known as the “high-value-slow-decrease” class, included 43 patients (8%) and was characterized by initially high PCT values that remained stable for the first three days before gradually declining. Class 2, the “consistent-low” class, included 354 patients (66%) and displayed low initial PCT values that remained consistently low over the first 7 days in the ICU. Class 3, the “high-value-fast-decrease” class, included 140 patients (26%) and was marked by high initial PCT values that declined rapidly over time. Baseline characteristics differed significantly between the three PCT classes (Table 1). Patients in Class 1 and Class 3 had higher baseline SOFA scores and required more norepinephrine to maintain blood pressure compared to Class 2. In-hospital mortality was highest in Class 1 (42%) compared to Class 2 (32%) and Class 3 (24%) (P = 0.044). Baseline variables (age, sex, baseline SOFA, baseline lactate, presence of septic shock, surgical intervention, infection sites) and PCT classes were included in the Cox proportional hazards model for in-hospital mortality. With Class 1 as the reference level, Class 2 (HR: 0.507 [95% CI 0.287–0.895], P = 0.020) and Class 3 (HR 0.449 [95% CI 0.244–0.827], P = 0.011) were independent protective factors for in-hospital mortality. Kaplan–Meier survival curves were used to illustrate the in-hospital mortality of the 3 classes (Fig. 1B).

Fig. 1
Abstract Image

A Shows the 3 distinct procalcitonin classes. B Contains Kaplan–Meier curves for patients in the 3 classes. Class 1: “high-value-slow-decrease” class; Class 2: “consistent-low” class; Class 3: “high-value-fast-decrease” class

Full size image
Table 1 Comparison of baseline characteristics among the three PCT classes
Full size table

Three distinct PCT trajectories were identified in this study. Despite notable baseline differences across the classes, the “high-value-slow-decrease” PCT trajectory is an independent risk factor for higher in-hospital mortality. Given the strong link between PCT trajectories and mortality, continuous monitoring of PCT levels is essential for clinicians to detect potential high-risk sepsis patients. The insights from this study provide clinicians with information to optimize clinical decision-making and may support the development of more personalized and effective sepsis management strategies, ultimately benefiting patient outcomes.

The datasets generated and/or analysed during the current study are not publicly available due to containing information that could compromise the privacy of research participants, but are available from the corresponding authors, JS and MZ, on reasonable request.

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This research received funding from Shanghai municipal hospital diagnosis and treatment technology promotion and optimization management project (SHDC22022203).

Authors and Affiliations

  1. Department of Critical Care Medicine, Zhongshan Hospital of Fudan University, No. 180, Fenglin Road, Xuhui District, Shanghai, China

    Xu Wang, Shilong Lin, Ming Zhong & Jieqiong Song

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Contributions

XW was responsible for the methodological design, coordination, data preparation, and statistical analysis. SL contributed to data collection and statistical analysis. XW drafted and revised the manuscript. JS and MZ conceived and designed the study and assisted in drafting the paper. XW, SL, MZ, and JS contributed to the preparation and critical review of the manuscript. All authors approved the final manuscript.

Corresponding authors

Correspondence to Ming Zhong or Jieqiong Song.

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The authors declare no competing interests.

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Wang, X., Lin, S., Zhong, M. et al. The procalcitonin trajectory as an effective tool for identifying sepsis patients at high risk of mortality. Crit Care 28, 312 (2024). https://doi.org/10.1186/s13054-024-05100-0

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降钙素原轨迹是识别脓毒症高危患者的有效工具
败血症是一种危重病,给全球医疗系统带来沉重负担。鉴于败血症患者的异质性,识别高危死亡人群至关重要[1]。降钙素原(PCT)是评估败血症严重程度和指导抗生素治疗的公认生物标志物[2]。实际上,PCT 通常在住院期间反复测量。虽然单一的 PCT 值很有帮助,但通过重复测量得出的动态趋势能更深入地了解患者的预后。传统的分析方法往往无法完全捕捉到这些数据的复杂性[3]。通过采用分层线性混合效应(HLME)模型[4],本研究旨在探索脓毒症患者不同的 PCT 变化轨迹及其与死亡率的关系,为风险分层提供一种完善的方法。复旦大学附属中山医院医学伦理委员会审查并批准了本研究(B2021-501R)。由于本研究为回顾性研究,且分析使用的是匿名临床数据,因此免除了知情同意。在2019年1月至2024年3月期间,共纳入537例患者(女性167例,男性370例;中位年龄69岁[IQR 59-77])。脓毒性休克患者占 47.5%。腹部(274/51.0%)和呼吸道(202/37.6%)是两个主要感染部位。在重症监护室的中位住院时间(LOS)为 10 天 [IQR 4-20],住院时间为 15 天 [IQR 10-25]。共有 2492 个 PCT 测量值可用于轨迹模型分析。使用 HLME 模型确定了三个等级(图 1A)。第 1 类也称为 "高值-缓慢下降 "类,包括 43 名患者(8%),其特点是最初的 PCT 值较高,在前三天保持稳定,然后逐渐下降。第 2 类是 "持续低值 "类,包括 354 名患者(66%),其初始 PCT 值较低,在重症监护室的前 7 天内持续保持低值。第 3 类是 "高值-快速下降 "类,包括 140 名患者(占 26%),其特点是初始 PCT 值较高,但随着时间的推移迅速下降。三个 PCT 等级的基线特征差异很大(表 1)。与 2 级相比,1 级和 3 级患者的基线 SOFA 评分较高,需要更多去甲肾上腺素来维持血压。与 2 级(32%)和 3 级(24%)相比,1 级患者的院内死亡率最高(42%)(P = 0.044)。基线变量(年龄、性别、基线 SOFA、基线乳酸、是否存在脓毒性休克、手术干预、感染部位)和 PCT 分级被纳入院内死亡率的 Cox 比例危险模型。以 1 级为参考水平,2 级(HR:0.507 [95% CI 0.287-0.895],P = 0.020)和 3 级(HR 0.449 [95% CI 0.244-0.827],P = 0.011)是院内死亡率的独立保护因素。图 1A 显示了 3 个不同的降钙素原等级。B 包含 3 个等级患者的 Kaplan-Meier 曲线。1 级:"高值-缓慢-下降 "级;2 级:"持续-低值 "级;3 级:"高值-快速-下降 "级图片全尺寸表 1 三个 PCT 级之间基线特征的比较表格全尺寸本研究确定了三种不同的 PCT 轨迹。尽管各等级之间存在明显的基线差异,但 "高值-慢减 "PCT轨迹是导致较高院内死亡率的独立风险因素。鉴于 PCT 轨迹与死亡率之间的密切联系,临床医生必须持续监测 PCT 水平,以发现潜在的高危脓毒症患者。这项研究为临床医生提供了优化临床决策的信息,并有助于制定更个性化、更有效的脓毒症管理策略,最终改善患者的预后。Evans L, Rhodes A, Alhazzani W, Antonelli M, Coopersmith CM, French C, Machado FR, McIntyre L, Ostermann M, Prescott HC, et al. Surviving sepsis campaign: International guidelines for management of sepsis and septic shock 2021.Intensive Care Med.2021;47(11):1181-247.Article PubMed PubMed Central Google Scholar Papp M, Kiss N, Baka M, Trásy D, Zubek L, Fehérvári P, Harnos A, Turan C, Hegyi P, Molnár Z. Procalcitonin-guided antibiotic therapy may shorten length of treatment and may improve survival-a systematic review and meta-analysis.Crit Care.2023;27(1):394.
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来源期刊
Critical Care
Critical Care 医学-危重病医学
CiteScore
20.60
自引率
3.30%
发文量
348
审稿时长
1.5 months
期刊介绍: Critical Care is an esteemed international medical journal that undergoes a rigorous peer-review process to maintain its high quality standards. Its primary objective is to enhance the healthcare services offered to critically ill patients. To achieve this, the journal focuses on gathering, exchanging, disseminating, and endorsing evidence-based information that is highly relevant to intensivists. By doing so, Critical Care seeks to provide a thorough and inclusive examination of the intensive care field.
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