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Effect of therapeutic plasma exchange on antimicrobials in critically ill patients
Critical Care ( IF 8.8 ) Pub Date : 2024-08-28 , DOI: 10.1186/s13054-024-05077-w
Ugur Balaban 1 , Emre Kara 1 , Esat Kivanc Kaya 2 , Osman Ilhami Ozcebe 3 , Murat Akova 4 , Arzu Topeli 2 , Kaya Yorganci 5 , Kutay Demirkan 1
Affiliation  

Dear Editor,

Therapeutic plasma exchange (TPE) is a procedure in which plasma is separated from the cellular components of whole blood by various methods. The removed plasma is replaced with albumin or fresh frozen plasma (FFP). TPE aims to eliminate disease-related pathogens [1]. Removal of significant amounts of plasma during TPE can alter the pharmacokinetic profiles of antimicrobials, resulting in inadequate therapeutic efficacy. In addition, critically ill patients may have altered pharmacokinetic profiles for many drugs. Data on antimicrobial elimination via TPE in intensive care unit (ICU) patients are scarce. Few studies have examined the effect of TPE on antimicrobials [2].

Several factors may influence antimicrobial elimination during TPE. High plasma protein-binding (> 80%) and low volume of distribution (Vd < 0.2 L/kg) are important pharmacokinetic factors indicating a high rate of removal via TPE [3]. Studies have also shown that allowing an adequate interval for drug distribution significantly decreases drug elimination via TPE [4]. It is important to note that distribution half-life values are not typically available to clinicians through drug monographs. However, because the distribution phase generally has a shorter half-life than the elimination phase, elimination half-life data can be used as a surrogate measure of drug distribution half-life [5].

We report the plasma levels of meropenem, teicoplanin, voriconazole, and amikacin immediately before and after TPE, along with the amounts of antimicrobials in plasmapheresate (removed plasma) from three critically ill ICU patients. All antimicrobials were at steady-state during TPE sessions, with none given immediately before or during TPE. TPE was performed using the Spectra Optia Apheresis System (TERUMOBCT) by continuous-flow-centrifugation. Plasma levels of these drugs are routinely monitored at our hospital using liquid chromatography with tandem mass spectrometry (LC–MS/MS). The amount of drug removed (mg) (QTPE) was calculated as follows: drug concentration in plasmapheresate (mg/L) x volume of plasma removed (L). To the best of our knowledge, this study is the first to provide data on the effect of TPE on steady-state plasma levels of meropenem, teicoplanin, and amikacin, as well as the first to report on the effect of TPE on the disposition of amikacin.

A 40-year-old male patient with hemochromatosis, chronic liver disease, type 2 diabetes, and atrial fibrillation was admitted to the medical ICU for neutropenic fever and community-acquired pneumonia (Case 1). He underwent 7 TPE sessions with FFP to treat worsening hyperbilirubinemia associated with hepatic encephalopathy. The patient's antimicrobial therapy included meropenem for neutropenic fever, teicoplanin for gram-positive pathogens due to epididymitis, and voriconazole for Aspergillus fumigatus. Maintenance doses were meropenem 2 g q8h as a prolonged infusion, teicoplanin 12 mg/kg q24h (after a loading dose of 12 mg/kg q12h for 3 doses), and voriconazole 4 mg/kg q12h (after a loading dose of 6 mg/kg q12h). The QTPE ranged from 35.64 to 43.22 mg for meropenem, 12.03 mg to 51.86 mg for teicoplanin, and 29.62 mg to 51.68 mg for voriconazole after the 4th, 5th and 6th TPE sessions. Antifungal therapy was changed to liposomal amphotericin B due to supratherapeutic voriconazole levels. The patient's clinical improvement was unaffected by the amount of antimicrobial eliminated, allowing the patient to complete his treatment.

A 76-year-old female patient with myasthenia gravis, metastatic carcinoma, and hypertension was admitted to the medical ICU for a myasthenic crisis (Case 2). She underwent 7 TPE sessions with albumin. The patient was treated with meropenem for hospital-acquired pneumonia caused by extended-spectrum β-lactamase-producing Klebsiella pneumonia. Meropenem was administered at a maintenance dose of 2 g q8h as a prolonged infusion (3-h) after the loading dose. The QTPE for meropenem was 27.39 mg after the 6th TPE session. Based on the culture results, antibacterial therapy was escalated to trimethoprim-sulfamethoxazole on day 5 of meropenem treatment.

A 67-year-old male patient with non-Hodgkin's lymphoma, pancreatic adenocarcinoma, and type 2 diabetes was admitted to the surgical ICU for neurological deterioration (Case 3). He underwent 15 TPE sessions with FFP to treat hyperbilirubinemia associated with hepatic encephalopathy. Amikacin was prescribed at a dose of 15 mg/kg q24h for the treatment of å sepsis associated with intra-abdominal infection. The QTPE for amikacin was 23.53 mg after the 14th TPE session. The patient passed away due to cardiac arrest while on amikacin therapy.

Detailed clinical data and TPE parameters for the three patients are presented in Tables 1 and 2.

Table 1 Clinical data and pre-TPE laboratory values of the patients undergoing TPE sessions
Full size table
Table 2 Plasma exchange parameters and drug concentration measurements in patients with TPE
Full size table

In the present study, we assumed adequate time for tissue distribution of meropenem, teicoplanin and amikacin based on their elimination half-lives. For meropenem, this resulted in a QTPE range of 27.39 mg to 43.22 mg, with 1.37% to 2.16% after a single administered dose. The QTPE for meropenem in our study is lower than that reported in a previous study of patients receiving a 1 g dose of meropenem by 1-h infusion concurrent with TPE, resulting in a mean QTPE of 142.23 ± 110.31 mg [6]. These differences may be explained by differing intervals for drug distribution. Similarly, the QTPE of teicoplanin in the first patient ranged from 12.03 to 51.86 mg, with 1.25% to 5.4% of the single administered dose removed. Again, this is substantially lower compared to a previous study 12 patients who received intravenous teicoplanin at a dose of 6 mg/kg immediately prior to TPE, resulting in a mean QTPE of 74.6 ± 34.6 mg [7].

The amount of voriconazole removed in the plasmapheresate ranged from 29.62 to 51.68 mg, with 9.26% to 16.15% of the single administered dose removed. In a case study where TPE was initiated following a 1-h voriconazole infusion, the calculated QTPE was approximately 10.1 mg [8]. The voriconazole plasma level in our first patient was 18.1 mg/L on the non-TPE day between the 4th and 5th TPE sessions. There were no drug interactions with voriconazole. Plasma voriconazole levels were unexpectedly high for unknown reasons. These high levels may have affected our measurements.

The current report is also the first to report on the effect of TPE on amikacin, showing a QTPE of 23.53 mg, with 2.09% of the single administered dose removed. Low protein-binding affinity and a 21.6-h interval from the end of infusion to TPE may be related to measurements.

Ibrahim et al. [3] propose that the most reliable method to assess the effect of TPE on drug disposition is to measure the amount of drug removed in the plasmapheresate. In the presented cases, the amount of drug removed via TPE was not significant in comparison to the administered single dose, as shown in Table 2. Therefore, it can be stated that all antimicrobials in our study were minimally affected via TPE.

In conclusion, the results of this real-world study emphasize that attention should be paid to the timing of drug distribution, allowing sufficient time between drug administration and TPE to minimize antimicrobial elimination. In addition, therapeutic drug monitoring may help to improve antimicrobial management during TPE in critically ill patients.

No datasets were generated or analysed during the current study.

  1. Connelly-Smith L, Alquist CR, Aqui NA, et al. Guidelines on the use of therapeutic apheresis in clinical practice - evidence-based approach from the writing committee of the American society for apheresis: the ninth special issue. J Clin Apher. 2023;38(2):77–278.

    Article PubMed Google Scholar

  2. Krzych LJ, Czok M, Putowski Z. Is antimicrobial treatment effective during therapeutic plasma exchange? Investigating the role of possible interactions. Pharmaceutics. 2020. https://doi.org/10.3390/pharmaceutics12050395.

    Article PubMed PubMed Central Google Scholar

  3. Ibrahim RB, Liu C, Cronin SM, et al. Drug removal by plasmapheresis: an evidence-based review. Pharmacotherapy. 2007;27(11):1529–49. https://doi.org/10.1592/phco.27.11.1529.

    Article CAS PubMed Google Scholar

  4. Ibrahim RB, Balogun RA. Medications in patients treated with therapeutic plasma exchange: prescription dosage, timing, and drug overdose. Semin Dial. 2012;25(2):176–89. https://doi.org/10.1111/j.1525-139X.2011.01030.x.

    Article PubMed Google Scholar

  5. Mahmoud SH, Buhler J, Chu E, Chen SA, Human T. Drug dosing in patients undergoing therapeutic plasma exchange. Neurocrit Care. 2021;34(1):301–11. https://doi.org/10.1007/s12028-020-00989-1.

    Article CAS PubMed Google Scholar

  6. Jaruratanasirikul S, Neamrat P, Jullangkoon M, Samaeng M. Impact of therapeutic plasma exchange on meropenem pharmacokinetics. Pharmacotherapy. 2022;42(8):659–66. https://doi.org/10.1002/phar.2717.

    Article CAS PubMed Google Scholar

  7. Alet P, Lortholary O, Fauvelle F, et al. Pharmacokinetics of teicoplanin during plasma exchange. Clin Microbiol Infect. 1999;5(4):213–8. https://doi.org/10.1111/j.1469-0691.1999.tb00126.x.

    Article CAS PubMed Google Scholar

  8. Vay M, Foerster KI, Mahmoudi M, Seessle J, Mikus G. No alteration of voriconazole concentration by plasmapheresis in a critically ill patient. Eur J Clin Pharmacol. 2019;75(2):287–8. https://doi.org/10.1007/s00228-018-2582-6.

    Article PubMed Google Scholar

  9. Pistolesi V, Morabito S, Di Mario F, Regolisti G, Cantarelli C, Fiaccadori E. A guide to understanding antimicrobial drug dosing in critically ill patients on renal replacement therapy. Antimicrob Agents Chemother. 2019. https://doi.org/10.1128/AAC.00583-19.

    Article PubMed PubMed Central Google Scholar

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Authors and Affiliations

  1. Department of Clinical Pharmacy, Faculty of Pharmacy, Hacettepe University, Ankara, Turkey

    Ugur Balaban, Emre Kara & Kutay Demirkan

  2. Division of Intensive Care Medicine, Department of Internal Medicine, Faculty of Medicine, Hacettepe University, Ankara, Turkey

    Esat Kivanc Kaya & Arzu Topeli

  3. Division of Hematology, Department of Internal Medicine, Faculty of Medicine, Hacettepe University, Ankara, Turkey

    Osman Ilhami Ozcebe

  4. Department of Infectious Diseases and Clinical Microbiology, Faculty of Medicine, Hacettepe University, Ankara, Turkey

    Murat Akova

  5. Department of General Surgery, Faculty of Medicine, Hacettepe University, Ankara, Turkey

    Kaya Yorganci

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Contributions

U.B. was a major contributor in conceptualization, methodology, data analysis, and writing-original draft. E.K. contributed to conceptualization, methodology, and writing-review&editing. E.K.K., O.I.O., M.A., A.T., K.Y., and K.D. contributed to resources and writing-review&editing. All authors read and approved the final manuscript.

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Correspondence to Ugur Balaban.

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Ethical approval was not required. Informed consent was obtained from the patients.

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The authors declare no competing interests.

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Balaban, U., Kara, E., Kaya, E.K. et al. Effect of therapeutic plasma exchange on antimicrobials in critically ill patients. Crit Care 28, 280 (2024). https://doi.org/10.1186/s13054-024-05077-w

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中文翻译：

治疗性血浆置换对危重患者抗菌药物的影响

 尊敬的编辑：


治疗性血浆置换 （TPE） 是通过各种方法将血浆与全血的细胞成分分离的过程。用白蛋白或新鲜冰冻血浆 （FFP） 替代去除的血浆。TPE 旨在消除与疾病相关的病原体 [1]。在 TPE 过程中去除大量血浆会改变抗菌药物的药代动力学特征，导致治疗效果不足。此外，危重患者可能改变了许多药物的药代动力学特征。关于重症监护病房 （ICU） 患者通过 TPE 消除抗菌药物的数据很少。很少有研究检查 TPE 对抗菌剂的影响 [2]。


有几个因素可能会影响 TPE 期间的抗菌药物消除。高血浆蛋白结合 （> 80%） 和低分布容积 （Vd < 0.2 L/kg） 是重要的药代动力学因素，表明通过 TPE 去除率高 [3]。研究还表明，允许药物分配有足够的间隔会显着减少通过 TPE 消除的药物 [4]。需要注意的是，临床医生通常无法通过药物专论获得分布半衰期值。然而，由于分布期的半衰期通常短于消除期，因此消除半衰期数据可以作为药物分布半衰期的替代指标 [5]。


我们报告了 TPE 前后美罗培南、替考拉宁、伏立康唑和阿米卡星的血浆水平，以及 3 名危重 ICU 患者的血浆置换物（去除的血浆）中的抗菌药物量。在 TPE 疗程期间，所有抗菌剂都处于稳态，在 TPE 之前或期间没有立即给予。使用 Spectra Optia 单采系统 （TERUMOBCT） 通过连续流离心进行 TPE。我们医院使用液相色谱-串联质谱法 （LC-MS/MS） 常规监测这些药物的血浆水平。去除的药物量 （mg） （QTPE） 计算如下：血浆置换物中的药物浓度 （mg/L） x 去除的血浆体积 （L）。据我们所知，这项研究是第一个提供有关 TPE 对美罗培南、替考拉宁和阿米卡星稳态血浆水平影响的数据，也是第一个报告 TPE 对阿米卡星处置影响的研究。


一名 40 岁男性血色病、慢性肝病、2 型糖尿病和心房颤动患者因中性粒细胞减少性发热和社区获得性肺炎入住内科 ICU （病例 1）。他接受了 7 次 FFP TPE 治疗，以治疗与肝性脑病相关的恶化的高胆红素血症。患者的抗菌治疗包括美罗培南治疗中性粒细胞减少性发热、替考拉宁治疗附睾炎引起的革兰氏阳性病原体和伏立康唑治疗烟曲霉。维持剂量为美罗培南 2 g q8h 作为长期输注，替考拉宁 12 mg/kg q24h （负荷剂量为 12 mg/kg q12h 后，持续 3 剂）和伏立康唑 4 mg/kg q12h （负荷剂量为 6 mg/kg q12h后）。在第 4 次、第 5 次和第 6 次 TPE 疗程后，美罗培南的 QTPE 范围为 35.64 至 43.22 mg，替考拉宁为 12.03 mg 至 51.86 mg，伏立康唑为 29.62 mg 至 51.68 mg。由于超治疗性的伏立康唑水平，抗真菌治疗改为脂质体两性霉素 B。患者的临床改善不受消除的抗菌药物量的影响，使患者能够完成治疗。


一名 76 岁女性重症肌无力、转移性癌和高血压患者因肌无力危象入住内科 ICU （病例 2）。她接受了 7 次白蛋白 TPE 疗程。患者接受美罗培南治疗由超广谱 β-内酰胺酶克雷伯菌肺炎引起的医院获得性肺炎。美罗培南以 2 g q8h 的维持剂量给药，作为负荷剂量后延长输注 （3-h）。第 6 次 TPE 治疗后美罗培南的 QTPE 为 27.39 mg。根据培养结果，在美罗培南治疗第 5 天将抗菌治疗升级为甲氧苄啶-磺胺甲噁唑。


一名 67 岁男性非霍奇金淋巴瘤、胰腺癌和 2 型糖尿病患者因神经功能恶化入住外科 ICU （病例 3）。他接受了 15 次 FFP TPE 治疗，以治疗与肝性脑病相关的高胆红素血症。阿米卡星的剂量为 15 mg/kg q24h，用于治疗与腹腔内感染相关的 å 败血症。第 14 次 TPE 治疗后，阿米卡星的 QTPE 为 23.53 mg。患者在接受阿米卡星治疗期间因心脏骤停去世。


表 1 和表 2 列出了三名患者的详细临床数据和 TPE 参数。


表 1 接受 TPE 治疗的患者的临床数据和 TPE 前实验室值
 全尺寸表格

表 2 TPE 患者的血浆置换参数和药物浓度测量
 全尺寸表格


在本研究中，我们根据美罗培南、替考拉宁和阿米卡星的组织分布假设它们有足够的时间。对于美罗培南，这导致 QTPE 范围为 27.39 毫克至 43.22 毫克，单次给药后为 1.37% 至 2.16%。我们研究中美罗培南的 QTPE 低于之前一项研究中报道的，该研究的患者通过 1 小时输注 1 小时同时接受 TPE 给药，导致平均 QTPE 为 142.23 ± 110.31 毫克 [6]。这些差异可能是由药物分布的不同区间来解释的。同样，第一例患者替考拉宁的 QTPE 范围为 12.03 至 51.86 mg，单次给药剂量的 1.25% 至 5.4% 被去除。同样，与之前的研究 12 例患者相比，这要低得多，这些患者在 TPE 之前立即接受了 6 mg/kg 剂量的静脉注射替考拉宁，导致平均 QTPE 为 74.6 ± 34.6 mg [7]。


血浆置换物中去除的伏立康唑量为 29.62 至 51.68 mg，去除了单次给药剂量的 9.26% 至 16.15%。在一项案例研究中，在伏立康唑输注 1 小时后开始 TPE，计算出的 QTPE 约为 10.1 mg [8]。我们第一位患者的伏立康唑血浆水平在第 4 次和第 5 次 TPE 治疗之间的非 TPE 日为 18.1 mg/L。与伏立康唑没有药物相互作用。血浆伏立康唑水平出乎意料地高，原因不明。这些高水平可能影响了我们的测量。


目前的报告也是第一个报告 TPE 对阿米卡星影响的报告，显示 QTPE 为 23.53 毫克，去除了 2.09% 的单次给药剂量。低蛋白质结合亲和力和从输注结束到 TPE 的 21.6 小时间隔可能与测量有关。


Ibrahim 等人 [3] 提出，评估 TPE 对药物处置影响的最可靠方法是测量血浆置换物中去除的药物量。在所介绍的病例中，与给药的单剂量相比，通过 TPE 去除的药物量并不显着，如 表 2 所示。因此，可以说我们研究中的所有抗菌剂都受到 TPE 的影响最小。


总之，这项真实世界研究的结果强调，应注意药物分配的时间，在给药和 TPE 之间留出足够的时间，以尽量减少抗菌药物的消除。此外，治疗药物监测可能有助于改善危重患者 TPE 期间的抗菌管理。


在当前研究期间没有生成或分析数据集。


  1. Connelly-Smith L、Alquist CR、Aqui NA 等人。在临床实践中使用治疗性血液分离的指南 - 来自美国血液分离学会写作委员会的循证方法：第九期特刊。J Clin Apher。2023;38(2):77–278.


    文章 PubMed 谷歌学术


  2. 文章： PubMed PubMed Central Google Scholar


  3. Ibrahim RB、Liu C、Cronin SM 等人。通过血浆置换去除药物：一项循证综述。药物。2007;27(11):1529–49.https://doi.org/10.1592/phco.27.11.1529。


    论文 CAS PubMed Google Scholar


  4. 易卜拉欣 RB，巴洛贡 RA。接受治疗性血浆置换治疗的患者的药物：处方剂量、时间和药物过量。Semin Dial. 2012 年;25(2):176–89.https://doi.org/10.1111/j.1525-139X.2011.01030.x。


    文章 PubMed 谷歌学术


  5. 论文 CAS PubMed Google Scholar


  6. Jaruratanasirikul S， Neamrat P， Jullangkoon M， Samaeng M. 治疗性血浆置换对美罗培南药代动力学的影响。药物。2022;42(8):659–66.https://doi.org/10.1002/phar.2717。


    论文 CAS PubMed Google Scholar


  7. Alet P、Lortholary O、Fauvelle F 等人。血浆置换过程中替考拉宁的药代动力学。Clin Microbiol 感染。1999;5(4):213–8.https://doi.org/10.1111/j.1469-0691.1999.tb00126.x。


    论文 CAS PubMed Google Scholar


  8. 文章 PubMed 谷歌学术


  9. 文章： PubMed PubMed Central Google Scholar

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 作者和单位


  1. 土耳其安卡拉 Hacettepe 大学药学院临床药学系


    乌古尔·巴拉班、埃姆雷·卡拉和库塔伊·德米尔坎


  2. 土耳其安卡拉哈塞特佩大学医学院内科重症监护医学科

    Esat Kivanc Kaya & Arzu Topeli


  3. 土耳其安卡拉 Hacettepe 大学医学院内科血液学部

     奥斯曼·伊尔哈米·奥兹切贝


  4. 土耳其安卡拉 Hacettepe 大学医学院传染病和临床微生物学系

     穆拉特·阿科娃


  5. 土耳其安卡拉 Hacettepe 大学医学院普通外科系

     卡娅·约尔甘奇

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 贡献


U.B. 是概念化、方法论、数据分析和撰写原始草稿的主要贡献者。E.K. 为概念化、方法论以及写作审查和编辑做出了贡献。E.K.K.、O.I.O.、M.A.、A.T.、K.Y. 和 K.D. 为资源和写作审查和编辑做出了贡献。所有作者都阅读并批准了最终稿件。

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 引用本文


Balaban， U.， Kara， E.， Kaya， EK 等人。治疗性血浆置换对危重患者抗菌药物的影响。Crit Care28， 280 （2024）。https://doi.org/10.1186/s13054-024-05077-w

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  • DOI：https://doi.org/10.1186/s13054-024-05077-w

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更新日期：2024-08-28
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