Filippo Mariano, Alberto Mella, Domenico Greco’, Luigi Biancone
{"title":"Sorbents therapies in burn patients with septic shock on continuous kidney replacement therapy: an added value for a selected population","authors":"Filippo Mariano, Alberto Mella, Domenico Greco’, Luigi Biancone","doi":"10.1186/s13054-025-05284-z","DOIUrl":null,"url":null,"abstract":"<p>We read with great interest the review addressing the issue of the use of extracorporeal blood purification therapies in sepsis [1]. We congratulate the authors for their excellent work. There are issues that we want to highlight and comment on.</p><p>The authors highlighted the extreme difficulty in demonstrating the effectiveness of these therapies in large randomized studies, with mortality as the primary end-point. Practical experience teaches that in critically ill patients the effectiveness, in terms of survival, of some therapeutic approaches with great clinical impact (volume filling, the use of diuretics, extracorporeal replacement treatment, and so on) can be very different from patient to patient, resulting in the same treatment being beneficial to one patient, and not beneficial, or even deleterious for another patient. Treatment must be directed at targets tailored for the individual patient, not at common target values that may be appropriate for some but certainly not for all [2].</p><p>Among these therapies, the potential benefits of coupled-plasma filtration adsorption (CPFA) were first documented in patients with Acute Kidney Injury (AKI) on Continuous Kidney Replacement Therapy (CKRT) [1] and later confirmed in a cohort of burn ICU patients undergoing CKRT [3]. A significant reduction in mortality was observed in the group of 39 burn patients treated with CKRT-CPFA, compared to the group of 87 patients treated with CKRT alone (51.3% and 77.1%, respectively). Then, the next Compact-2 study, which compared patients with septic shock treated with CKRT-CPFA (CPFA-CKRT group) as an adjunctive therapy and patients who did not receive it (control group), could not confirm the benefit. The study was prematurely stopped because of a suspected excess of early mortality in the CPFA-treated group, particularly present in the CPFA-CKRT group among patients without renal failure, who would not have required per se the renal replacement therapy [1]. As an explanation of these surprising results, it has been hypothesized that extracorporeal therapy could eliminate a significant portion of antibiotics, particularly when an absorptive component was associated with it. Concerning a life-saving antibiotic such as colistin, during CPFA-CKRT plasma perfusion was very efficient in removing the drug, as the post-cartridge colistin concentration was not detectable [3, 4]. Therefore, CPFA could be harmful to subject a patient with septic shock but good renal function. Because of CPFA-CKRT doubling the purifying function some substances such as antibiotic therapy at standard dosage could be eliminated at an excessive rate [1, 4].</p><p>Nowadays CytoSorb® is one of the most promising sorbent therapy currently available for septic shock. Recently it has been documented that in burn patients on CKRT with septic shock, and poorly responsive to therapy, an additive CytoSorb® treatment was associated with an improvement in clinical outcome and reduced in-hospital mortality in comparison with subjects treated with CKRT alone [5]. The application of CytoSorb® took place in a very dispersed way over the time of admission. Out of 11 patients, 7 started the CKRT together with the sorbent application, and 2 patients needed repetitive cycles, with additional treatments. Cytosorb® was tailored to the clinical condition of every single patient, applying a repetitive cycle of treatment following several septic shock episodes.</p><p>It is conceivable that the sorbent technologies acting as a rescue therapy were able to overcome the microvascular derangement related to septic shock, it reaches stabilization of patient hemodynamics, and so time was gained for the other crucial interventions for burn patient's survival such as surgery and antibiotics [5].</p><p>As already underlined, the selection of patients and the time of intervention may be crucial for demonstrating the efficacy and clinical impact of a new treatment option in ICU patients [2]. In this scenario, burn patients are a particular population, in which the initial injury is defined in its pathophysiological characteristics, and quantifiable in its severity, probability of sepsis, and death. In large trials involving generic ICU patients, these conditions are lacking, many potential confounding factors can influence the result, such as the use in unselected patient populations, variability in demographic characteristics, comorbidities, use of medication, time since disease onset, source of the infection, or duration of therapy.</p><p>As in the past likely occurred, the introduction of innovative therapies in ICU patients led to \"throwing the baby out with the bath water\". Judiciously applying these new therapies in very controlled conditions and selected populations may be the only correct way forward.</p><p>No datasets were generated or analysed during the current study.</p><dl><dt style=\"min-width:50px;\"><dfn>CPFA:</dfn></dt><dd>\n<p>Coupled-plasma filtration adsorption</p>\n</dd><dt style=\"min-width:50px;\"><dfn>AKI:</dfn></dt><dd>\n<p>Acute kidney injury</p>\n</dd><dt style=\"min-width:50px;\"><dfn>CKRT:</dfn></dt><dd>\n<p>Continuous kidney replacement therapy</p>\n</dd></dl><ol data-track-component=\"outbound reference\" data-track-context=\"references section\"><li data-counter=\"1.\"><p>Bottari G, Ranieri VM, Ince C, Pesenti A, Aucella F, Scandroglio AM, Ronco C, Vincent JL. Use of extracorporeal blood purification therapies in sepsis: the current paradigm, available evidence, and future perspectives. Crit Care. 2024;28(1):432. https://doi.org/10.1186/s13054-024-05220-7.</p><p>Article PubMed PubMed Central Google Scholar </p></li><li data-counter=\"2.\"><p>Vincent JL. Recent negative clinical trials in septic patients: maybe a good thing? Minerva Anestesiol. 2015;81(2):122–4.</p><p>PubMed Google Scholar </p></li><li data-counter=\"3.\"><p>Mariano F, Hollo’ Z, Depetris N, Malvasio V, Mella A, Bergamo D, Pensa A, Berardino M, Stella M, Biancone L. Coupled-plasma filtration and adsorption for severe burn patients with septic shock and acute kidney injury treated with renal replacement therapy. Burns. 2020;46(1):190–8. https://doi.org/10.1016/j.burns.2019.05.017.</p><p>Article PubMed Google Scholar </p></li><li data-counter=\"4.\"><p>Mariano F, Leporati M, Carignano P, Stella M, Vincenti M, Biancone L. Efficient removal of colistin A and B in critically ill patients undergoing CVVHDF and sorbent technologies. J Nephrol. 2015;28(5):623–31. https://doi.org/10.1007/s40620-014-0143-3.</p><p>Article PubMed Google Scholar </p></li><li data-counter=\"5.\"><p>Mariano F, Greco’ D, Depetris N, Mella A, Sciarrillo A, Stella M, Berardino M, Risso D, Gambino R, Biancone L. CytoSorb® in burn patients with septic shock and acute kidney injury on continuous kidney replacement therapy is associated with improved clinical outcome and survival. Burns. 2024;50(5):1213–22. https://doi.org/10.1016/j.burns.2024.02.028.</p><p>Article PubMed 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>Not applicable.</p><p>This work was supported by the Italian Ministry of University and Research (MIUR, ex 60%, Rilo 2024 to FM). The authors declare no financial interest.</p><h3>Authors and Affiliations</h3><ol><li><p>Nephrology, Dialysis and Transplantation U, AOU City of Health and Science, CTO Hospital, Via G. Zuretti 29, 10126, Turin, Italy</p><p>Filippo Mariano, Alberto Mella & Luigi Biancone</p></li><li><p>Department of Medical Sciences, University of Turin, Corso AM Dogliotti, 10126, Turin, Italy</p><p>Filippo Mariano, Alberto Mella, Domenico Greco’ & Luigi Biancone</p></li></ol><span>Authors</span><ol><li><span>Filippo Mariano</span>View author publications<p>You can also search for this author in <span>PubMed<span> </span>Google Scholar</span></p></li><li><span>Alberto Mella</span>View author publications<p>You can also search for this author in <span>PubMed<span> </span>Google Scholar</span></p></li><li><span>Domenico Greco’</span>View author publications<p>You can also search for this author in <span>PubMed<span> </span>Google Scholar</span></p></li><li><span>Luigi Biancone</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>F.M., A.M and D.G wrote the main manuscript text. F.M. and L.B. reviewed the final version of the manuscript.</p><h3>Corresponding author</h3><p>Correspondence to Filippo Mariano.</p><h3>Ethics approval and consent to participate</h3>\n<p>Not applicable.</p>\n<h3>Consent for publication</h3>\n<p>All authors give the consent to publish.</p>\n<h3>Competing interests</h3>\n<p>The authors declare that they have no competing interest.</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. 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/.</p>\n<p>Reprints and permissions</p><img alt=\"Check for updates. 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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>Mariano, F., Mella, A., Greco’, D. <i>et al.</i> Sorbents therapies in burn patients with septic shock on continuous kidney replacement therapy: an added value for a selected population. <i>Crit Care</i> <b>29</b>, 46 (2025). https://doi.org/10.1186/s13054-025-05284-z</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=\"2025-01-14\">14 January 2025</time></span></p></li><li><p>Accepted<span>: </span><span><time datetime=\"2025-01-16\">16 January 2025</time></span></p></li><li><p>Published<span>: </span><span><time datetime=\"2025-01-27\">27 January 2025</time></span></p></li><li><p>DOI</abbr><span>: </span><span>https://doi.org/10.1186/s13054-025-05284-z</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 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Abstract
We read with great interest the review addressing the issue of the use of extracorporeal blood purification therapies in sepsis [1]. We congratulate the authors for their excellent work. There are issues that we want to highlight and comment on.
The authors highlighted the extreme difficulty in demonstrating the effectiveness of these therapies in large randomized studies, with mortality as the primary end-point. Practical experience teaches that in critically ill patients the effectiveness, in terms of survival, of some therapeutic approaches with great clinical impact (volume filling, the use of diuretics, extracorporeal replacement treatment, and so on) can be very different from patient to patient, resulting in the same treatment being beneficial to one patient, and not beneficial, or even deleterious for another patient. Treatment must be directed at targets tailored for the individual patient, not at common target values that may be appropriate for some but certainly not for all [2].
Among these therapies, the potential benefits of coupled-plasma filtration adsorption (CPFA) were first documented in patients with Acute Kidney Injury (AKI) on Continuous Kidney Replacement Therapy (CKRT) [1] and later confirmed in a cohort of burn ICU patients undergoing CKRT [3]. A significant reduction in mortality was observed in the group of 39 burn patients treated with CKRT-CPFA, compared to the group of 87 patients treated with CKRT alone (51.3% and 77.1%, respectively). Then, the next Compact-2 study, which compared patients with septic shock treated with CKRT-CPFA (CPFA-CKRT group) as an adjunctive therapy and patients who did not receive it (control group), could not confirm the benefit. The study was prematurely stopped because of a suspected excess of early mortality in the CPFA-treated group, particularly present in the CPFA-CKRT group among patients without renal failure, who would not have required per se the renal replacement therapy [1]. As an explanation of these surprising results, it has been hypothesized that extracorporeal therapy could eliminate a significant portion of antibiotics, particularly when an absorptive component was associated with it. Concerning a life-saving antibiotic such as colistin, during CPFA-CKRT plasma perfusion was very efficient in removing the drug, as the post-cartridge colistin concentration was not detectable [3, 4]. Therefore, CPFA could be harmful to subject a patient with septic shock but good renal function. Because of CPFA-CKRT doubling the purifying function some substances such as antibiotic therapy at standard dosage could be eliminated at an excessive rate [1, 4].
Nowadays CytoSorb® is one of the most promising sorbent therapy currently available for septic shock. Recently it has been documented that in burn patients on CKRT with septic shock, and poorly responsive to therapy, an additive CytoSorb® treatment was associated with an improvement in clinical outcome and reduced in-hospital mortality in comparison with subjects treated with CKRT alone [5]. The application of CytoSorb® took place in a very dispersed way over the time of admission. Out of 11 patients, 7 started the CKRT together with the sorbent application, and 2 patients needed repetitive cycles, with additional treatments. Cytosorb® was tailored to the clinical condition of every single patient, applying a repetitive cycle of treatment following several septic shock episodes.
It is conceivable that the sorbent technologies acting as a rescue therapy were able to overcome the microvascular derangement related to septic shock, it reaches stabilization of patient hemodynamics, and so time was gained for the other crucial interventions for burn patient's survival such as surgery and antibiotics [5].
As already underlined, the selection of patients and the time of intervention may be crucial for demonstrating the efficacy and clinical impact of a new treatment option in ICU patients [2]. In this scenario, burn patients are a particular population, in which the initial injury is defined in its pathophysiological characteristics, and quantifiable in its severity, probability of sepsis, and death. In large trials involving generic ICU patients, these conditions are lacking, many potential confounding factors can influence the result, such as the use in unselected patient populations, variability in demographic characteristics, comorbidities, use of medication, time since disease onset, source of the infection, or duration of therapy.
As in the past likely occurred, the introduction of innovative therapies in ICU patients led to "throwing the baby out with the bath water". Judiciously applying these new therapies in very controlled conditions and selected populations may be the only correct way forward.
No datasets were generated or analysed during the current study.
CPFA:
Coupled-plasma filtration adsorption
AKI:
Acute kidney injury
CKRT:
Continuous kidney replacement therapy
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This work was supported by the Italian Ministry of University and Research (MIUR, ex 60%, Rilo 2024 to FM). The authors declare no financial interest.
Authors and Affiliations
Nephrology, Dialysis and Transplantation U, AOU City of Health and Science, CTO Hospital, Via G. Zuretti 29, 10126, Turin, Italy
Filippo Mariano, Alberto Mella & Luigi Biancone
Department of Medical Sciences, University of Turin, Corso AM Dogliotti, 10126, Turin, Italy
Filippo Mariano, Alberto Mella, Domenico Greco’ & Luigi Biancone
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F.M., A.M and D.G wrote the main manuscript text. F.M. and L.B. reviewed the final version of the manuscript.
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Mariano, F., Mella, A., Greco’, D. et al. Sorbents therapies in burn patients with septic shock on continuous kidney replacement therapy: an added value for a selected population. Crit Care29, 46 (2025). https://doi.org/10.1186/s13054-025-05284-z
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我们怀着极大的兴趣阅读了关于在脓毒症bbb中使用体外血液净化疗法的综述。我们祝贺作者们出色的工作。有些问题是我们想要强调和评论的。作者强调,在以死亡率为主要终点的大型随机研究中,证明这些疗法的有效性极其困难。实践经验告诉我们,在危重病人中,就生存而言,一些具有重大临床影响的治疗方法(容量填充、利尿剂的使用、体外替代治疗等)的有效性可能因病人而异,导致同样的治疗对一个病人有益,对另一个病人却没有好处,甚至有害。治疗必须针对个别患者量身定制的目标,而不是针对可能适合某些人但肯定不适合所有人的共同目标值。在这些疗法中,耦合血浆过滤吸附(CPFA)的潜在益处首先在急性肾损伤(AKI)患者连续肾替代治疗(CKRT)[3]中被证实,随后在一组接受CKRT[3]的烧伤ICU患者中得到证实。与单独使用CKRT治疗的87例患者相比,使用CKRT- cpfa治疗的39例烧伤患者死亡率显著降低(分别为51.3%和77.1%)。然后,下一项Compact-2研究比较了接受CKRT-CPFA作为辅助治疗的脓毒性休克患者(CPFA-CKRT组)和未接受ckfa治疗的患者(对照组),无法证实其益处。由于怀疑cpfa治疗组的早期死亡率过高,特别是在没有肾功能衰竭的CPFA-CKRT组中,这些患者本身不需要肾脏替代治疗bbb,因此研究过早停止。作为对这些令人惊讶的结果的解释,有人假设体外治疗可以消除很大一部分抗生素,特别是当吸收成分与之相关时。对于像粘菌素这样的救命抗生素,在CPFA-CKRT期间,血浆灌注对药物的去除非常有效,因为药筒后粘菌素浓度无法检测[3,4]。因此,CPFA可能对感染性休克但肾功能良好的患者有害。由于CPFA-CKRT加倍了净化功能,一些物质如标准剂量的抗生素治疗可能会以过高的速率被消除[1,4]。目前,CytoSorb®是目前感染性休克最有前途的吸收疗法之一。最近有文献表明,在接受CKRT治疗并感染性休克的烧伤患者中,与单独接受CKRT治疗的患者相比,加用CytoSorb®治疗与临床结果的改善和住院死亡率的降低相关[10]。在入学期间,CytoSorb®的应用以非常分散的方式进行。在11例患者中,7例患者在开始CKRT治疗时同时使用吸附剂,2例患者需要重复周期,并进行额外治疗。Cytosorb®是针对每个患者的临床情况量身定制的,在几次感染性休克发作后应用重复周期的治疗。可以想象,吸收剂技术作为一种抢救疗法,能够克服感染性休克相关的微血管紊乱,达到患者血流动力学的稳定,从而为手术和抗生素等其他对烧伤患者生存至关重要的干预措施赢得时间。正如已经强调的那样,患者的选择和干预时间可能是证明一种新的治疗方案对ICU患者的疗效和临床影响的关键。在这种情况下,烧伤患者是一个特殊的人群,其初始损伤是由其病理生理特征定义的,其严重程度、败血症的可能性和死亡是可量化的。在涉及普通ICU患者的大型试验中,缺乏这些条件,许多潜在的混杂因素可能影响结果,例如在未选择的患者群体中使用,人口统计学特征的可变性,合并症,药物使用,发病时间,感染源或治疗持续时间。正如过去可能发生的那样,在ICU患者中引入创新疗法导致“将婴儿连同洗澡水一起倒掉”。明智地将这些新疗法应用于非常受控的条件和选定的人群可能是唯一正确的前进道路。在本研究中没有生成或分析数据集。 CPFA:耦合血浆过滤吸附;aki:急性肾损伤;ckrt:持续肾替代治疗[j]。使用体外血液净化治疗败血症:目前的范例,现有的证据,和未来的前景。危重症护理,2024;28(1):432。https://doi.org/10.1186/s13054-024-05220-7.Article PubMed PubMed Central谷歌学者Vincent JL。最近败血症患者的临床试验阴性:也许是件好事?中华麻醉学杂志,2015;81(2):122-4。[PubMed]学者Mariano F, Hollo ' Z, Depetris N, Malvasio V, Mella A, Bergamo D, Pensa A, Berardino M, Stella M, Biancone L.肾替代疗法治疗严重烧伤合并感染性休克急性肾损伤患者的耦合血浆过滤吸附。烧伤。2020;46(1):190 - 8。https://doi.org/10.1016/j.burns.2019.05.017.Article PubMed bbb学者Mariano F, Leporati M, Carignano P, Stella M, Vincenti M, Biancone L. CVVHDF和吸附剂技术对危重患者粘菌素A和B的高效去除。中华眼科杂志,2015;28(5):623-31。https://doi.org/10.1007/s40620-014-0143-3.Article PubMed bbb学者Mariano F, Greco ' D, Depetris N, Mella A, sciarillo A, Stella M, Berardino M, Risso D, Gambino R, Biancone L. CytoSorb®在烧伤合并感染性休克和急性肾损伤患者持续肾脏替代治疗中的临床疗效和生存率的改善。烧伤。2024;(5):1213 - 22所示。https://doi.org/10.1016/j.burns.2024.02.028.Article PubMed谷歌学者下载参考资料不适用。这项工作得到了意大利大学和研究部(MIUR, ex 60%, Rilo 2024 to FM)的支持。作者声明没有经济利益。作者和单位:血液学,透析和移植U, AOU健康与科学城,CTO医院,Via G. Zuretti 29,10126,都灵,意大利Luigi biancone都灵大学医学部,Corso AM Dogliotti, 10126,都灵,意大利Luigi BianconeAuthorsFilippo MarianoView作者出版物您也可以在PubMed谷歌ScholarAlberto MellaView作者出版物中搜索此作者您也可以在PubMed谷歌ScholarDomenico Greco 'View作者出版物中搜索此作者您也可以在PubMed谷歌ScholarLuigi BianconeView作者出版物中搜索此作者您也可以在PubMed谷歌ScholarContributionsF.M中搜索此作者。, a.m.和d.g.撰写了主要的手稿文本。F.M.和L.B.审阅了手稿的最终版本。通讯作者:Filippo Mariano。对参与者的伦理批准和同意不适用。出版同意所有作者同意出版。竞争利益作者宣称他们没有竞争利益。出版商声明:对于已出版的地图和机构关系中的管辖权要求,普林格·自然保持中立。开放获取本文遵循知识共享署名-非商业-非衍生品4.0国际许可协议,该协议允许以任何媒介或格式进行非商业用途、共享、分发和复制,只要您适当注明原作者和来源,提供知识共享许可协议的链接,并注明您是否修改了许可材料。根据本许可协议,您无权分享源自本文或其部分内容的改编材料。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协议中,除非在材料的署名中另有说明。如果材料未包含在文章的知识共享许可中,并且您的预期用途不被法律法规允许或超过允许的用途,您将需要直接获得版权所有者的许可。要查看本许可协议的副本,请访问http://creativecommons.org/licenses/by-nc-nd/4.0/.Reprints和permissionsCite这篇文章mariano, F., Mella, a ., Greco ', D.等人。吸收剂治疗烧伤合并脓毒性休克患者的持续肾脏替代治疗:对选定人群的附加价值。危重护理29,46(2025)。https://doi.org/10.1186/s13054-025-05284-zDownload citation:收稿日期:2025年1月14日接受日期:2025年1月16日发布日期:2025年1月27日doi: https://doi.org/10.1186/s13054-025-05284-zShare这篇文章任何人与您分享以下链接将能够阅读此内容:获取可共享链接对不起,本文目前没有可共享链接。复制到剪贴板由施普林格自然共享内容倡议提供
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