The lonely glutamine tree in the middle of the infinite critically ill forest,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.)

The lonely glutamine tree in the middle of the infinite critically ill forest
Critical Care ( IF 8.8 ) Pub Date : 2021-09-17 , DOI: 10.1186/s13054-021-03743-x
Panagiotis Briassoulis ₁ , Stavroula Ilia ₁ , Efrossini Briassouli ₂ , Marianna Miliaraki ₁ , George Briassoulis ₁

Affiliation

Dear Editor,

We read with great interest the article by Dr. Smedberg et al. addressing the issue of plasma glutamine status at intensive care unit (ICU) admission [1]. As indicated in their paper, hyperglutaminemia (≥ 930 μmol/L) at admission is an independent mortality predictor. There are issues that we want to highlight and comment on.

First, in this cohort of patients, 85% had liver disease at admission. The study lacks a non-liver failure hyperglutaminemic and/or a liver-failure non-hyperglutaminemic control group to examine metabolic pathways, amino acid kinetics, and compared outcomes. In a recent study in critically ill patients enrolled from three ICUs in South Africa, 14.2% had high (median 898.9 µmol/L) plasma glutamine levels. Patients with a diagnosis of liver failure had the highest glutamine levels. In this study, mortality was higher in the low (< 420 μmol/L) compared to high (> 420 μmol/L) glutamine level (62.2% vs. 37.8%) [2]. We have previously demonstrated that high doses of L-alanine-glutamine or L-glutamine did not induce any of the T helper (Th)1, Th2, and Th17 cytokines in either healthy or septic human PBMCs at 4 and 24 h [3].

Second, the main finding of the study is that hyperglutaminemia at ICU admission was associated with a more than twofold higher mortality rate at six months (46%) compared to patients with normal or low plasma glutamine concentrations at admission (18%). But the high plasma glutamine concentration could have led to limit protein/amino acid intake in these patients. Why should an initial high glutamine level be associated with mortality at 6 months? The acute phase of critical illness is associated with variable patterns of plasma amino acid changes, characterized by decreasing, increasing trends, or no changes in plasma levels compared with the values found in healthy subjects [4]. As the disease progresses, the levels of different amino acids gradually decrease, increase, or fluctuate over time. We have previously shown that pediatric patients with septic shock (hospital mortality 22%) had lower levels of glutamine on ICU day 3 (410 vs. 726 μmol/L) and 5 (426 vs. 691 μmol/L), compared to patients with non-infectious critical illness (mortality 4%) [4].

Similar to other nutritional constituents, temporarily adapted to the acute phase of critical illness [5], hyperglutaminemia could have only been an epiphenomenon, obviously affected by acute liver damage at admission. Future explorations are thus encouraged to clarify the mechanisms underlying the metabolism of glutamine in critical illness-related organ failures.

Marie Smedberg,
Inga Tjäder,
Olav Rooyackers &
Jan Wernerman

Department of Anesthesiology and Intensive Care, CLINTEC, Karolinska Institute and Perioperative Medicine and Intensive Care, Karolinska University Hospital Huddinge, Stockholm, Sweden
Marie Smedberg, Inga Tjäder, Olav Rooyackers & Jan Wernerman

We thank Drs Briassoulis et al. for their interest in and comments on our recent publication [1]. As stated, the glutamine tree is indeed lonely in the infinite critically ill forest. The main reason for us to publish this piece of information was the lack of published materials over hyperglutaminemia in the adult critically ill population. Our first observation of admission hyperglutaminemia as a risk factor for mortality contained only 8 subjects [6]. The present study contains 26 subjects, or 19 subjects if the postoperative liver transplant patients with zero mortality are excluded. The small number of subjects makes statistical comparisons hazardous. In both these studies, we defined hyperglutaminemia for the critically ill as the cutoff (maximum of sensitivity + specificity) for 6-month mortality in a ROC curve including all study patients with an admission plasma glutamine value above the normal range for healthy subjects, which turned out to be identical (930 umol/L) in the two studies. The study by Blaauw et al. has a different design and contains a different patient cohort, but basically it confirms our results for the hyperglutaminemic subjects, although they use the upper normal level for healthy individuals to define hyperglutaminemia [2]. We agree with Drs Briassoulis et al. that prospective studies over the underlying mechanism behind the statistical connection between glutamine plasma concentrations and mortality outcomes in the critically ill are a future challenge for those of us that are interested in the “glutamine tree”.

Not applicable.

1.
Smedberg M, Helleberg J, Norberg Å, Tjäder I, Rooyackers O, Wernerman J. Plasma glutamine status at intensive care unit admission: an independent risk factor for mortality in critical illness. Crit Care. 2021;25:240. https://doi.org/10.1186/s13054-021-03640-3
Article Google Scholar
2.
Blaauw R, Nel DG, Schleicher GK. Plasma glutamine levels in relation to intensive care unit patient outcome. Nutrients. 2020;12:E402.
Article Google Scholar
3.
Briassouli E, Goukos D, Daikos G, Apostolou K, Routsi C, Nanas S, et al. Glutamine suppresses Hsp72 not Hsp90α and is not inducing Th1, Th2, or Th17 cytokine responses in human septic PBMCs. Nutrition. 2014;30:1185–94.
CAS Article Google Scholar
4.
Spanaki AM, Tavladaki T, Dimitriou H, Kozlov AV, Duvigneau JC, Meleti E, et al. Longitudinal profiles of metabolism and bioenergetics associated with innate immune hormonal inflammatory responses and amino-acid kinetics in severe sepsis and systemic inflammatory response syndrome in children. JPEN. 2018;42:1061–74.
CAS Article Google Scholar
5.
Briassoulis G, Ilia S. Vitamin D deficiency in sepsis: “body humors” imbalance or sepsis “epiphenomenon”? Crit Care Med. 2017;45:376–7.
Article Google Scholar
6.
Rodas PC, Rooyackers O, Hebert C, Norberg A, Wernerman J. Glutamine and glutathione at ICU admission in relation to outcome. Clin Sci. 2012;122(11–12):591–7.
CAS Article Google Scholar

Download references

None.

Not applicable.

Affiliations

Pediatric Intensive Care Unit, Postgraduate Program “Emergency and Intensive Care in Children Adolescents and Young Adults”, School of Medicine, University of Crete, Section 6D (delta), Office 03, Voutes, 71003, Heraklion, Crete, Greece
Panagiotis Briassoulis, Stavroula Ilia, Marianna Miliaraki & George Briassoulis
First Department of Internal Medicine - Propaedeutic, National and Kapodistrian University of Athens, Athens, Greece
Efrossini Briassouli

Authors

Panagiotis BriassoulisView author publications
You can also search for this author in PubMed Google Scholar
Stavroula IliaView author publications
You can also search for this author in PubMed Google Scholar
Efrossini BriassouliView author publications
You can also search for this author in PubMed Google Scholar
Marianna MiliarakiView author publications
You can also search for this author in PubMed Google Scholar
George BriassoulisView author publications
You can also search for this author in PubMed Google Scholar

Contributions

PB, SI, EB, MM, and GB have contributed in all parts in producing the manuscript. All authors read and approved the final manuscript.

Corresponding author

Correspondence to George Briassoulis.

Ethics approval and consent to participate

Not applicable.

Consent for publication

All authors give the consent to publish.

Competing interests

All authors claim no competing interest or conflict of interest.

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 4.0 International License, which permits use, sharing, adaptation, 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 changes were made. 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/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.

Reprints and Permissions

Cite this article

Briassoulis, P., Ilia, S., Briassouli, E. et al. The lonely glutamine tree in the middle of the infinite critically ill forest. Crit Care 25, 342 (2021). https://doi.org/10.1186/s13054-021-03743-x

Download citation

Received: 11 August 2021
Accepted: 12 August 2021
Published: 17 September 2021
DOI: https://doi.org/10.1186/s13054-021-03743-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：

无限重病林中的孤谷谷氨酰胺树

亲爱的编辑，

我们饶有兴趣地阅读了 Smedberg 博士等人的文章。解决重症监护病房 (ICU) 入院时血浆谷氨酰胺状态的问题 [1]。正如他们的论文中所指出的，入院时的高谷氨酰胺血症（≥ 930 μmol/L）是一个独立的死亡率预测因子。有些问题我们想强调和评论。

首先，在这组患者中，85% 的患者在入院时患有肝脏疾病。该研究缺乏非肝功能衰竭高谷氨酰胺和/或肝功能衰竭非高谷氨酰胺对照组来检查代谢途径、氨基酸动力学和比较结果。在最近对来自南非三个 ICU 的危重患者进行的一项研究中，14.2% 的患者血浆谷氨酰胺水平较高（中位数为 898.9 µmol/L）。诊断为肝功能衰竭的患者的谷氨酰胺水平最高。在这项研究中，低谷氨酰胺水平 (< 420 μmol/L) 的死亡率高于高 (> 420 μmol/L) 谷氨酰胺水平 (62.2% vs. 37.8%) [2]。我们之前已经证明，在 4 小时和 24 小时时，高剂量的 L-丙氨酸-谷氨酰胺或 L-谷氨酰胺不会在健康或败血症的人类 PBMC 中诱导任何 T 辅助 (Th)1、Th2 和 Th17 细胞因子 [3] .

其次，该研究的主要发现是，与入院时血浆谷氨酰胺浓度正常或低的患者 (18%) 相比，ICU 入院时的高谷氨酰胺血症与 6 个月时的死亡率 (46%) 高两倍以上。但高血浆谷氨酰胺浓度可能导致这些患者限制蛋白质/氨基酸的摄入。为什么初始高谷氨酰胺水平与 6 个月时的死亡率相关？危重疾病的急性期与血浆氨基酸变化的不同模式相关，与健康受试者中发现的值相比，其特征是血浆水平降低、增加或没有变化[4]。随着疾病的进展，不同氨基酸的水平随着时间的推移逐渐降低、增加或波动。

与其他营养成分相似，暂时适应了危重病的急性期 [5]，高谷氨酰胺血症可能只是一种附带现象，明显受到入院时急性肝损伤的影响。因此，鼓励未来的探索以阐明谷氨酰胺在危重疾病相关器官衰竭中的代谢机制。

玛丽·斯梅德伯格
英加·特亚德，
Olav Rooyackers &
扬·沃纳曼

麻醉科和重症监护科，CLINTEC，卡罗林斯卡研究所和围手术期医学和重症监护，卡罗林斯卡大学医院哈丁格，斯德哥尔摩，瑞典
Marie Smedberg、Inga Tjäder、Olav Rooyackers 和 Jan Wernerman

我们感谢 Briassoulis 博士等人。感谢他们对我们最近的出版物 [1] 的兴趣和评论。如前所述，谷氨酰胺树确实在无限的重病森林中孤独。我们发布这条信息的主要原因是缺乏关于成人危重患者高谷氨酰胺血症的已发表材料。我们对入院高谷氨酰胺血症作为死亡危险因素的首次观察仅包含 8 名受试者 [6]。本研究包含 26 名受试者，如果排除术后肝移植死亡率为零的患者，则为 19 名受试者。少数受试者使统计比较危险。在这两项研究中，我们将危重患者的高谷氨酰胺定义为 ROC 曲线中 6 个月死亡率的临界值（最大敏感性 + 特异性），包括所有入院血浆谷氨酰胺值高于健康受试者正常范围的研究患者，结果证明是相同的(930 umol/L) 在两项研究中。Blaauw 等人的研究。具有不同的设计并包含不同的患者队列，但基本上它证实了我们对高谷氨酰胺血症受试者的结果，尽管他们使用健康个体的正常上限水平来定义高谷氨酰胺血症 [2]。我们同意 Briassoulis 博士等人的观点。

不适用。

1.
Smedberg M、Helleberg J、Norberg Å、Tjäder I、Rooyackers O、Wernerman J. 重症监护病房入院时的血浆谷氨酰胺状态：危重病死亡率的独立危险因素。暴击护理。2021；25:240。https://doi.org/10.1186/s13054-021-03640-3
文章谷歌学术
2.
Blaauw R、Nel DG、Schleicher GK。与重症监护病房患者结果相关的血浆谷氨酰胺水平。营养素。2020；12：E402。
文章谷歌学术
3.
Briassouli E、Goukos D、Daikos G、Apostolou K、Routsi C、Nanas S 等。谷氨酰胺抑制 Hsp72 而不是 Hsp90α，并且不会在人脓毒症 PBMC 中诱导 Th1、Th2 或 Th17 细胞因子反应。营养。2014；30：1185-94。
CAS 文章 Google Scholar
4.
Spanaki AM、Tavladaki T、Dimitriou H、Kozlov AV、Duvigneau JC、Meleti E 等。与儿童严重脓毒症和全身炎症反应综合征的先天免疫激素炎症反应和氨基酸动力学相关的代谢和生物能量学的纵向分布。日本。2018 年；42：1061-74。
CAS 文章 Google Scholar
5.
Briassoulis G, Ilia S. 败血症中的维生素 D 缺乏：“体液”失衡或败血症“附带现象”？暴击护理医学。2017；45：376-7。
文章谷歌学术
6.
Rodas PC、Rooyackers O、Hebert C、Norberg A、Wernerman J. ICU 入住时的谷氨酰胺和谷胱甘肽与结果的关系。临床科学。2012;122(11–12):591–7。
CAS 文章 Google Scholar

下载参考

没有任何。

不适用。

隶属关系

儿科重症监护室，研究生课程“儿童青少年和年轻人的急诊和重症监护”，克里特大学医学院，第 6D 部分（三角洲），办公室 03，Voutes，71003，伊拉克利翁，克里特岛，希腊
Panagiotis Briassoulis、Stavroula Ilia、Marianna Miliaraki 和 George Briassoulis
第一内科 - Propaedeutic, National and Kapodistrian University of Athens, 雅典, 希腊
埃弗罗西尼·布里亚苏利

作者

Panagiotis Briassoulis查看作者出版物
您也可以在PubMed Google Scholar中搜索此作者
Stavroula Ilia查看作者出版物
您也可以在PubMed Google Scholar中搜索此作者
Efrossini Briassouli查看作者出版物
您也可以在PubMed Google Scholar中搜索此作者
Marianna Miliaraki查看作者出版物
您也可以在PubMed Google Scholar中搜索此作者
George Briassoulis查看作者出版物
您也可以在PubMed Google Scholar中搜索此作者

贡献

PB、SI、EB、MM 和 GB 在手稿的所有部分都做出了贡献。所有作者阅读并认可的终稿。

通讯作者

与乔治·布里亚索利斯的通信。

伦理批准和同意参与

不适用。

同意发表

所有作者均同意发表。

利益争夺

所有作者均声称没有竞争利益或利益冲突。

出版商说明

Springer Nature 对已发布地图和机构附属机构中的管辖权主张保持中立。

开放获取本文根据知识共享署名 4.0 国际许可协议获得许可，该许可允许以任何媒体或格式使用、共享、改编、分发和复制，只要您适当注明原作者和来源，提供链接到知识共享许可，并指出是否进行了更改。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，除非在材料的信用额度中另有说明。如果文章的知识共享许可中未包含材料，并且您的预期用途未得到法律法规的允许或超出允许的用途，则您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/4.0/。

重印和许可