Sex matters: Is it time for a SOFA makeover?,Critical Care

当前位置： X-MOL 学术 › Crit. Care › 论文详情

Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)

Sex matters: Is it time for a SOFA makeover?
Critical Care ( IF 8.8 ) Pub Date : 2024-08-08 , DOI: 10.1186/s13054-024-05030-x
Emma Larsson _{1,

2}

Affiliation

While sepsis affects individuals regardless of sex, emerging research has highlighted notable differences in how women and men experience, respond to, and recover from sepsis treated in intensive care units (ICU). These differences are influenced by a complex interplay of biological, hormonal, and sociocultural factors. As we explore sepsis management in ICU settings, it becomes evident that understanding the factors contributing to these sex-based variations is important for tailoring therapeutic approaches and improving overall patient outcomes. Moreover, for a nuanced interpretation of current evidence, it is worth noting the distinction between the terms gender and sex: gender refers to the socially constructed roles and behaviors that a given society considers appropriate, while sex pertains to biological characteristics.

The ICU sepsis patient population comprises individuals of all ages and with diverse comorbidities and clinical conditions, leading to acute organ failure. Efforts have been made to identify distinct phenotypes and establish correlations with host-response patterns and clinical outcomes [1]. As clinicians, it is increasingly clear that personalized treatment and prognostication strategies are essential for optimizing patient care, but somewhat limited by our current diagnostic and therapeutic tools. While patient sex is often a readily available characteristic, the extent to which we incorporate it as a variable into our comprehensive clinical assessments for critically ill sepsis patients could warrant further consideration and refinement. Are we taking it into account as thoroughly as we should? In their recent publication in this journal, Zimmermann and colleagues conducted a retrospective study on sex differences in the sequential organ failure assessment (SOFA) score among ICU patients with sepsis or septic shock, analyzing data from 85 ICUs across Switzerland [2]. They concluded that significant variations exist, although the full clinical implications remain to be elucidated. Notably, they found no disparity in ICU mortality rates between male and female patients. The authors suggested that reevaluation of sex-specific thresholds for SOFA score components could potentially refine future individualized classifications, addressing a current oversight in the consideration of patient sex within the SOFA scoring system.

Aligned with these findings, emerging insights into sepsis pathophysiology indicate that sex-based differences in host responses to pathogens may play an important role [3]. Animal models suggest that females exhibit lower susceptibility to sepsis and tend to recover more effectively than males. Distinct host responses to pathogens between females and males could be partly attributed to the sex-specific polarization of intracellular pathways responding to pathogen–cell receptor interactions [4]. Sex hormones are believed to play a role in these disparities and have been shown to target most immune cells, yet the full range of contributing factors remains a subject of ongoing investigation. Further exploration is warranted to fully understand how various factors beyond sex hormones influence the observed differences in immune reactions [3].

Current evidence does not allow for definitive conclusions regarding the association between patient sex and sepsis-related mortality. In recent years, the sepsis literature has reported more favorable outcomes for women, less favorable outcomes, or no differences between women and men [5]. Differences in mortality, favoring either women or men, have also been observed for other ICU diagnoses [6, 7]. Establishing substantive evidence linking sex differences in clinical outcomes from animal models has proven challenging. Moreover, beyond therapeutic efforts in the ICU, other factors important for disease severity and recovery can differ between women and men. For example, health-seeking behaviors, such as the timing of seeking medical care, can influence outcomes by affecting the severity of sepsis upon ICU admission. Additionally, the roles of caregiving and social support structures are crucial factors influencing recovery trajectories and psychological outcomes following an ICU stay. These multifaceted elements collectively shape the overall impact of sepsis and underscore the need for further research, while also highlighting the complexity of understanding and addressing sex-related disparities.

Since its introduction, the SOFA score has been crucial in intensive care settings and sepsis management by quantifying the severity of organ dysfunction [8]. In their publication, Zimmerman and colleagues reported sex-specific differences in SOFA, particularly in the laboratory-based components [2]. However, the data must be interpreted with some caution considering potential bias. For example, creatinine levels inherently vary between women and men, and including additional variables such as patient weight could enhance interpretations of the analyses. Nevertheless, their findings raise a difficult question: could potential discrepancies in scoring of organ dysfunction hamper clinical decision-making regarding the appropriate level of care?

There is an underlying assumption in society and healthcare that critically ill patients are admitted to an ICU based primarily on illness severity and comorbidities, with other variables considered less relevant. It is therefore troublesome that we do not fully understand the sex discrepancy in the ICU population, where the distribution is consistently found to be around 40% women and 60% men [9, 10]. Current evidence is weak to guide whether we are, in fact, treating the adequate proportions of women and men. Given women’s longer life expectancy compared to men, yet often similar outcomes post-intensive care for sepsis, it prompts a reassessment of whether we are treating the appropriate proportions, also suggested by other authors [11, 12]. Should we consider admitting more, or fewer, women? Admittance patterns are inherently challenging to address in a scientific setting. Effort have been made in survey format to explore potential bias in admitting female versus male patients, but no detectable differences were found [13]. The results are obviously hindered by lack of sensitivity and a high risk of volunteer bias. Another interesting area for future research involves how age should be accounted for when addressing outcomes after intensive care, especially among older patients. Patient sex may influence age-associated outcomes, as has been discussed, for example, in the context of sepsis patients [14]. Considering sex-based differences in life expectancy, should equal mortality rates post-intensive care in older patients be interpretated as truly “equal”, given women’s longer life expectancy?

In conclusion, the complexities of sex-based differences in critically ill sepsis patients underscore the need for continued research to better understand these disparities, refine clinical scoring and prognostication, and optimize care for both women and men in the ICU.

Not applicable.

ICU:: Intensive care unit
SOFA:: Sequential organ failure assessment

Seymour CW, Kennedy JN, Wang S, Chang C-CH, Elliott CF, Xu Z, et al. Derivation, Validation, and Potential Treatment Implications of Novel Clinical Phenotypes for Sepsis. JAMA. 2019;321(20):2003. https://doi.org/10.1001/jama.2019.5791.
Article CAS PubMed PubMed Central Google Scholar
Zimmermann T, Kaufmann P, Amacher SA, Sutter R, Loosen G, Merdji H, et al. Sex differences in the SOFA score of ICU patients with sepsis or septic shock: a nationwide analysis. Crit Care. 2024. https://doi.org/10.1186/s13054-024-04996-y.
Article PubMed PubMed Central Google Scholar
Klein SL, Flanagan KL. Sex differences in immune responses. Nat Rev Immunol. 2016;16(10):626–38.
Article CAS PubMed Google Scholar
Lakbar I, Einav S, Lalevee N, Martin-Loeches I, Pastene B, Leone M. Interactions between Gender and Sepsis-Implications for the Future. Microorganisms. 2023;11(3):746.
Article CAS PubMed PubMed Central Google Scholar
Antequera A, Lopez-Alcalde J, Stallings E, Muriel A, Fernández Félix B, Del Campo R, et al. Sex as a prognostic factor for mortality in critically ill adults with sepsis: a systematic review and meta-analysis. BMJ Open. 2021;11(9):e048982.
Article PubMed PubMed Central Google Scholar
Zettersten E, Engerström L, Bell M, Jäderling G, Mårtensson J, Block L, et al. Long-term outcome after intensive care for COVID-19: differences between men and women-a nationwide cohort study. Crit Care. 2021;25(1):86.
Article PubMed PubMed Central Google Scholar
Fisher T, Hill N, Kalakoutas A, Lahlou A, Rathod K, Proudfoot A, et al. Sex differences in treatments and outcomes of patients with cardiogenic shock: a systematic review and epidemiological meta-analysis. Crit Care. 2024. https://doi.org/10.1186/s13054-024-04973-5.
Article PubMed PubMed Central Google Scholar
Vincent JL, Moreno R, Takala J, Willatts S, De Mendonça A, Bruining H, et al. The SOFA (Sepsis-related Organ Failure Assessment) score to describe organ dysfunction/failure. Intensive Care Med. 1996;22(7):707–10.
Article CAS PubMed Google Scholar
Modra LJ, Higgins AM, Abeygunawardana VS, Vithanage RN, Bailey MJ, Bellomo R. Sex differences in treatment of adult intensive care patients: a systematic review and meta-analysis. Crit Care Med. 2022;50(6):913–23.
Article PubMed Google Scholar
Samuelsson C, Sjoberg F, Karlstrom G, Nolin T, Walther SM. Gender differences in outcome and use of resources do exist in Swedish intensive care, but to no advantage for women of premenopausal age. Crit Care. 2015;19:129.
Article PubMed PubMed Central Google Scholar
Arslani K, Tontsch J, Todorov A, Gysi B, Kaufmann M, Kaufmann F, et al. Temporal trends in mortality and provision of intensive care in younger women and men with acute myocardial infarction or stroke. Crit Care. 2023;27(1):14.
Article PubMed PubMed Central Google Scholar
Todorov A, Kaufmann F, Arslani K, Haider A, Bengs S, Goliasch G, et al. Gender differences in the provision of intensive care: a Bayesian approach. Intensive Care Med. 2021;47(5):577–87.
Article PubMed PubMed Central Google Scholar
Zettersten E, Jäderling G, Larsson E, Bell M. The impact of patient sex on intensive care unit admission: a blinded randomized survey. Sci Rep. 2019;9(1):14222.
Article PubMed PubMed Central Google Scholar
Ko R-E, Kang D, Cho J, Na SJ, Chung CR, Lim SY, et al. Influence of gender on age-associated in-hospital mortality in patients with sepsis and septic shock: a prospective nationwide multicenter cohort study. Crit Care. 2023;27(1):229.
Article PubMed PubMed Central Google Scholar

Download references

None.

Authors and Affiliations

Department of Perioperative Medicine and Intensive Care, Karolinska University Hospital, Stockholm, Sweden
Emma Larsson
Department of Physiology and Pharmacology, Karolinska Institute, Stockholm, Sweden
Emma Larsson

Authors

Emma LarssonView author publications
You can also search for this author in PubMed Google Scholar

Contributions

E.L. responsible for the entire manuscript.

Corresponding author

Correspondence to Emma Larsson.

Ethics approval and consent to participate

Not applicable.

Consent for publication

Not applicable.

Competing interests

The author declares no competing interests.

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Open Access 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. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by-nc-nd/4.0/.

Reprints and permissions

Cite this article

Larsson, E. Sex matters: Is it time for a SOFA makeover?. Crit Care 28, 268 (2024). https://doi.org/10.1186/s13054-024-05030-x

Download citation

Received: 07 July 2024
Accepted: 09 July 2024
Published: 08 August 2024
DOI: https://doi.org/10.1186/s13054-024-05030-x

Share this article

Anyone you share the following link with will be able to read this content:

Sorry, a shareable link is not currently available for this article.

Provided by the Springer Nature SharedIt content-sharing initiative

中文翻译：

性很重要：是时候改造 SOFA 了吗？

虽然脓毒症影响个体，不分性别，但新兴研究强调，女性和男性在重症监护病房（ICU）治疗脓毒症的经历、反应和恢复方式存在显著差异。这些差异受到生物、荷尔蒙和社会文化因素复杂相互作用的影响。当我们探索 ICU 环境中的脓毒症管理时，很明显，了解导致这些基于性别的变异的因素对于定制治疗方法和改善整体患者预后非常重要。此外，为了对当前证据进行细致的解释，值得注意的是性别和性别这两个术语之间的区别：性别是指特定社会认为适当的社会建构的角色和行为，而性则与生物特征有关。

ICU 脓毒症患者群体包括所有年龄段的个体，具有不同的合并症和临床状况，导致急性器官衰竭。已经努力确定不同的表型，并建立与宿主反应模式和临床结局的相关性 [1]。作为临床医生，越来越明显的是，个性化治疗和预后策略对于优化患者护理至关重要，但在某种程度上受到我们当前诊断和治疗工具的限制。虽然患者性别通常是一个现成的特征，但我们在多大程度上将其作为一个变量纳入对危重症脓毒症患者的综合临床评估中，可能需要进一步考虑和改进。我们是否尽可能彻底地考虑了它？Zimmermann 及其同事最近在该杂志上发表的文章中，对脓毒症或感染性休克 ICU 患者序贯器官衰竭评估（SOFA）评分的性别差异进行了回顾性研究，分析了来自瑞士 85 个 ICU 的数据 [2]。他们得出结论，存在显著差异，尽管完整的临床意义仍有待阐明。值得注意的是，他们发现男性和女性患者之间的 ICU 死亡率没有差异。作者建议，重新评估 SOFA 评分组成部分的性别特异性阈值可能会改进未来的个体化分类，解决当前 SOFA 评分系统中考虑患者性别的疏忽。

与这些发现相一致的是，对脓毒症病理生理学的新见解表明，宿主对病原体反应的性别差异可能起着重要作用[3]。动物模型表明，雌性对脓毒症的易感性较低，并且往往比雄性更有效地恢复。雌性和雄性之间不同的宿主对病原体的反应可能部分归因于响应病原体-细胞受体相互作用的细胞内通路的性别特异性极化 [4]。性激素被认为在这些差异中发挥作用，并且已被证明可以靶向大多数免疫细胞，但所有影响因素仍然是一个正在进行的研究主题。有必要进一步探索以充分了解性激素以外的各种因素如何影响观察到的免疫反应差异 [3]。

目前的证据无法就患者性别与脓毒症相关死亡率之间的关联得出明确的结论。近年来，脓毒症文献报道了女性结局更有利、结局较差或女性与男性之间无差异 [5]。在其他 ICU 诊断中也观察到死亡率差异，有利于女性或男性 [6， 7]。事实证明，建立将动物模型临床结果中的性别差异联系起来的实质性证据具有挑战性。此外，除了 ICU 的治疗工作外，其他对疾病严重程度和恢复很重要的因素在女性和男性之间可能有所不同。例如，寻求健康的行为，例如寻求医疗护理的时间，可以通过影响入住 ICU 时脓毒症的严重程度来影响结果。此外，护理和社会支持结构的作用是影响 ICU 住院后恢复轨迹和心理结果的关键因素。这些多方面的因素共同塑造了脓毒症的整体影响，强调了进一步研究的必要性，同时也突出了理解和解决性别相关差异的复杂性。

自推出以来，SOFA 评分通过量化器官功能障碍的严重程度，在重症监护机构和脓毒症管理中发挥了关键作用 [8]。在他们的出版物中，Zimmerman 及其同事报告了 SOFA 的性别特异性差异，尤其是在基于实验室的成分中 [2]。但是，考虑到潜在的偏差，必须谨慎解释数据。例如，女性和男性之间的肌酐水平本质上存在差异，包括患者体重等其他变量可以增强对分析的解释。然而，他们的研究结果提出了一个难题：器官功能障碍评分的潜在差异是否会妨碍关于适当护理水平的临床决策？

社会和医疗保健中有一个基本假设，即危重患者入住 ICU 主要基于疾病严重程度和合并症，其他变量被认为相关性较低。因此，我们没有完全了解 ICU 人群的性别差异是很麻烦的，那里的分布始终约为 40% 的女性和 60% 的男性 [9， 10]。目前的证据不足以指导我们是否真的在治疗足够的女性和男性比例。鉴于女性的预期寿命比男性长，但脓毒症重症监护后的结果往往相似，这促使我们重新评估我们是否治疗了适当的比例，其他作者也提出了这一建议[11,12]。我们应该考虑招收更多还是更少的女性？在科学环境中解决导入模式本身就具有挑战性。已努力以调查形式探讨女性患者与男性患者入院时的潜在偏倚，但未发现可检测到的差异 [13]。结果显然受到缺乏敏感性和志愿者偏倚高风险的阻碍。未来研究的另一个有趣领域涉及在处理重症监护后的结果时应如何考虑年龄，尤其是在老年患者中。患者性别可能影响年龄相关结局，例如在脓毒症患者中讨论过[14]。考虑到基于性别的预期寿命差异，鉴于女性的预期寿命更长，老年患者重症监护后死亡率相等是否应解释为真正“相等”？

总之，危重症脓毒症患者基于性别的差异的复杂性强调了持续研究的必要性，以更好地了解这些差异，完善临床评分和预后，并优化 ICU 中女性和男性的护理。

不適用。

重症监护室：: 重症监护病房
沙发：: 序贯器官衰竭评估

Seymour CW， Kennedy JN， Wang S， Chang C-CH， Elliott CF， Xu Z， et al. 脓毒症新临床表型的推导、验证和潜在治疗意义。美国医学会。2019;321(20):2003.https://doi.org/10.1001/jama.2019.5791。

论文： CAS PubMed， PubMed， Central Google Scholar
文章： PubMed PubMed Central Google Scholar
Klein SL， Flanagan KL. 免疫反应的性别差异。Nat Rev 免疫学。2016;16(10):626–38.

论文 CAS PubMed Google Scholar
Lakbar I， Einav S， Lalevee N， Martin-Loeches I， Pastene B， Leone M. 性别与脓毒症之间的相互作用——对未来的影响。微生物。2023;11(3):746.

论文： CAS PubMed， PubMed， Central Google Scholar
Antequera A、Lopez-Alcalde J、Stallings E、Muriel A、Fernández Félix B、Del Campo R 等人。性别是脓毒症危重成人患者死亡率的预后因素：系统评价和荟萃分析。BMJ 公开赛。2021;11（9）：e048982。

文章： PubMed PubMed Central Google Scholar
Zettersten E， Engerström L， Bell M， Jäderling G， Mårtensson J， Block L， et al.COVID-19 重症监护后的长期结果：男性和女性之间的差异 - 一项全国性的队列研究。暴击护理。2021;25(1):86.

文章： PubMed PubMed Central Google Scholar
文章： PubMed PubMed Central Google Scholar
Vincent JL、Moreno R、Takala J、Willatts S、De Mendonça A、Bruining H 等人。描述器官功能障碍/衰竭的 SOFA （脓毒症相关器官衰竭评估）评分。重症监护医学 1996 年;22(7):707–10.

论文 CAS PubMed Google Scholar
Modra LJ， Higgins AM， Abeygunawardana VS， Vithanage RN， Bailey MJ， Bellomo R. 成年重症监护患者治疗的性别差异：系统评价和荟萃分析。Crit Care Med. 2022;50(6):913–23.

文章 PubMed 谷歌学术
瑞典重症监护中确实存在结局和资源使用的性别差异，但对绝经前妇女没有好处。暴击护理。2015;19:129.

文章： PubMed PubMed Central Google Scholar
Arslani K、Tontsch J、Todorov A、Gysi B、Kaufmann M、Kaufmann F 等人。患有急性心肌梗死或中风的年轻女性和男性死亡率和重症监护提供的时间趋势。暴击护理。2023;27(1):14.

文章： PubMed PubMed Central Google Scholar
Todorov A、Kaufmann F、Arslani K、Haider A、Bengs S、Goliasch G 等人。提供重症监护的性别差异：贝叶斯方法。重症监护医学 2021;47(5):577–87.

文章： PubMed PubMed Central Google Scholar
Zettersten E， Jäderling G， Larsson E， Bell M. 患者性别对重症监护病房收治的影响：一项盲法随机调查。Sci Rep. 2019;9(1):14222.

文章： PubMed PubMed Central Google Scholar
Ko R-E， Kang D， Cho J， Na SJ， Chung CR， Lim SY， et al.性别对脓毒症和感染性休克患者年龄相关院内死亡率的影响：一项前瞻性全国性多中心队列研究。暴击护理。2023;27(1):229.

文章： PubMed PubMed Central Google Scholar

下载参考资料

没有。

作者和单位

瑞典斯德哥尔摩卡罗林斯卡大学医院围手术期医学和重症监护科
艾玛·拉尔森
瑞典斯德哥尔摩卡罗林斯卡学院生理学和药理学系
艾玛·拉尔森

作者

艾玛·拉尔森查看作者出版物

您也可以在 PubMed Google Scholar 中搜索此作者

贡献

E.L. 负责整个手稿。

通讯作者

与 Emma Larsson 的通信。

道德批准和参与同意

不適用。

同意发布

不適用。

利益争夺

作者声明没有利益冲突。

出版商注

施普林格·自然（Springer Nature）对已发布的地图和机构隶属关系中的管辖权主张保持中立。

开放获取本文根据 Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License 获得许可，该许可允许以任何媒体或格式进行任何非商业用途、共享、分发和复制，前提是您给予原作者和来源适当的署名，提供指向 Creative Commons 许可的链接，并说明您是否修改了许可材料。根据本许可，您无权共享源自本文或其部分的改编材料。本文中的图像或其他第三方材料包含在文章的知识共享许可中，除非在材料的致谢行中另有说明。如果材料未包含在文章的 Creative Commons 许可中，并且您的预期用途未被法律法规允许或超出允许的用途，您将需要直接从版权所有者处获得许可。要查看此许可证的副本，请访问 http://creativecommons.org/licenses/by-nc-nd/4.0/。

重印本和权限