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Volatile anaesthetics for ICU sedation: beyond hypnosis?
Critical Care ( IF 8.8 ) Pub Date : 2024-11-15 , DOI: 10.1186/s13054-024-05163-z
José Manuel Añón, Fernando Suarez-Sipmann, María Paz Escuela, Aris Perez-Lucendo, Andoni García-Muñoz

We read the review by Müller-Wirtz [1] et al., recently published in this journal with interest. It addresses the advantages of using volatile anaesthetics for lung and diaphragm-protective sedation. As the authors point out in their methodology, it is a narrative review based on expert opinion to which we wanted to contribute with some comments we believe are important.

The authors affirm that volatile anaesthetics reduce tidal volume and simultaneously increase respiratory rate in a dose-dependent fashion, thus potentially contributing to reduce lung stress and strain in spontaneously breathing patients. In addition, volatile anaesthetics better preserve respiratory drive than do common intravenous alternatives. The combination of these two effects lead them to conclude that volatile anaesthetics may contribute to a lung-diaphragmatic protective ventilation. Attributing a lung-diaphragmatic protective effect to the use of one specific type of sedation based mainly on pre-clinical studies [2,3,4,5,6] and small studies on healthy volunteers [7,8,9,10,11] with little data on critically ill patients, is a hypothesis that warrants to be tested and confirmed in well-designed clinical trials. We agree on the importance of adequate sedation and the potential protective benefits of volatile anaesthetics, but the role of factors such as the underlying lung condition, the effective control of respiratory drive and the dosage needed for it, the synergistic effects with opioids and other hypnotics, among others are yet to be established. The best balance between a preserved or excessive respiratory drive is difficult and depends on the individual patient and may vary along the evolution. For instance, in the presence of a high respiratory drive, such as seen in patients with acute respiratory distress syndrome (ARDS), sedation should rather contribute to modulate the intensity of the spontaneous inspiratory effort than to enhance it. Nevertheless, volatile anaesthetics are a welcome new addition to the clinical arsenal to improve sedation strategies in the always complicated transition from controlled to spontaneous mechanical ventilation.

All reflectors increase dead space ventilation due to their internal volume and partial carbon dioxide reflection. The two devices clinically available for inhaled sedation have made an effort to reduce their instrumental dead space volume, on average from 100 ml in the first-generation devices to around 50 ml of the currently used ones. However, it is important to pay special attention to avoid unnecessary increases in dead space particularly in patients ventilated with lower tidal volumes, where instrumental dead-space can add up to a 15–30% to the dead-space fraction. In this respect, the graphical abstract used to illustrate the clinical setup is rather unfortunate showing a large straight connector adding an additional instrumental dead space volume of at least 50–70 ml something that should be strictly avoided when using volatile anaesthetics. Patients need to compensate for this effect by increasing minute ventilation (either tidal volume, respiratory rate or both), all potentially contributing to lung injury, which can outweigh the intended protective effect in terms of a reduction in lung’s mechanical stress [12].

In summary, the first step to consider regarding the use of isoflurane in critically ill patients is to weigh its benefits as a hypnotic, an attractive alternative, at least in the short term. Although its long-term effects and outcomes compared to other intravenous hypnotics in critically ill patients remain unclear, isoflurane appears to be increasingly used in ICUs. Some scientific societies consider isoflurane a first-line sedative for ventilated patients requiring moderate or deep sedation due to its short duration of action and safety profile. But their recommendations emphasize the importance of adequately training ICU healthcare personnel to optimize its administration and minimize associated risks [13]. Other potential benefits are yet to be demonstrated. Currently, comparative studies with propofol are being conducted in patients requiring sedation for more than 48 h, focusing on outcomes such as delirium or length of mechanical ventilation. The possibility that isoflurane may reduce stress and strain in patients with spontaneous breathing or have a protective effect on the lung and diaphragm is a very attractive hypothesis that requires confirmation in clinical trials in the critical care setting.

The authors declare no competing interests.

No datasets were generated or analysed during the current study.

Müller-Wirtz LM, O´Gara B, Gama de Abreu M, Schultz MJ, Beitler JR, Jerath A, et al. Volatile anaesthetics for lung- and diaphragm-protective sedation. Crit Care. 2024;28:269.
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Authors and Affiliations

Department of Intensive Care Medicine, Hospital Universitario La Paz, Paseo de La Castellana 261, 28046, Madrid, Spain
José Manuel Añón & Andoni García-Muñoz
Instituto de Investigación del Hospital Universitario La Paz, IdiPAZ, Madrid, Spain
José Manuel Añón & Andoni García-Muñoz
Centro de Investigación Biomédica en Red de Enfermedades Respiratorias (CIBERES), Instituto de Salud Carlos III, Madrid, Spain
José Manuel Añón & Fernando Suarez-Sipmann
Department of Intensive Care Medicine, Hospital Universitario La Princesa, Madrid, Spain
Fernando Suarez-Sipmann & Aris Perez-Lucendo
Department of Intensive Care Medicine , Hospital Universitario Infanta Leonor, Madrid, Spain
María Paz Escuela

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José Manuel AñónView author publications
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Fernando Suarez-SipmannView author publications
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María Paz EscuelaView author publications
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Aris Perez-LucendoView author publications
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Andoni García-MuñozView author publications
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Contributions

JMA, FSS, MPE, APL and AGM contributed to the initial concept and design. JMA and FSS participated in the final draft of the manuscript. All authors read and approved the final manuscript.

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Correspondence to José Manuel Añón.

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Añón, J.M., Suarez-Sipmann, F., Escuela, M.P. et al. Volatile anaesthetics for ICU sedation: beyond hypnosis?. Crit Care 28, 369 (2024). https://doi.org/10.1186/s13054-024-05163-z

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Received: 02 November 2024
Accepted: 06 November 2024
Published: 15 November 2024
DOI: https://doi.org/10.1186/s13054-024-05163-z

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中文翻译：

用于 ICU 镇静的挥发性麻醉剂：催眠之外？

我们饶有兴趣地阅读了最近发表在本杂志上的 Müller-Wirtz [1] 等人的评论。它解决了使用挥发性麻醉剂进行肺和隔膜保护性镇静的优势。正如作者在他们的方法中指出的那样，这是一篇基于专家意见的叙述性综述，我们希望为它做出贡献，并提供一些我们认为重要的评论。

作者确认，挥发性麻醉剂可减少潮气量，同时以剂量依赖性方式增加呼吸频率，从而可能有助于减轻自主呼吸患者的肺应激和劳损。此外，挥发性麻醉剂比普通的静脉注射麻醉剂更能保持呼吸驱动。这两种作用的结合使他们得出结论，挥发性麻醉剂可能有助于肺-膈肌保护性通气。将肺-横膈膜保护作用归因于使用一种特定类型的镇静剂，主要基于临床前研究 [2,3,4,5,6] 和对健康志愿者的小型研究 [7,8,9,10,11]，而危重患者的数据很少，这是一个值得在精心设计的临床试验中进行测试和确认的假设。我们同意充分镇静的重要性和挥发性麻醉剂的潜在保护作用，但诸如潜在的肺部状况、呼吸驱动的有效控制及其所需的剂量、与阿片类药物和其他催眠药的协同作用等因素的作用尚未确定。在保留或过度呼吸驱动之间取得最佳平衡是困难的，并且取决于个体患者，并且可能会随着进化而变化。例如，在存在高呼吸驱动力的情况下，例如在急性呼吸窘迫综合征（ARDS）患者中看到的，镇静应该有助于调节自主吸气努力的强度，而不是增强它。尽管如此，挥发性麻醉剂是临床武器库中一个受欢迎的新成员，用于改进从受控机械通气到自主机械通气的复杂过渡中的镇静策略。

所有反射器由于其内部体积和部分二氧化碳反射而增加了死腔通风。临床上可用于吸入镇静的两种设备已努力减少其仪器死腔体积，平均从第一代设备的 100 毫升减少到目前使用的 50 毫升左右。然而，重要的是要特别注意避免死腔不必要地增加，尤其是在通气量较低的患者中，其中器械死腔加起来可增加 15-30% 的死腔分数。在这方面，用于说明临床设置的图形摘要相当遗憾，显示了一个大的直连接器增加了至少 50-70 ml 的额外器械死腔体积，在使用挥发性麻醉剂时应严格避免这种情况。患者需要通过增加每分钟通气量（潮气量、呼吸频率或两者兼而有之）来补偿这种影响，所有这些都可能导致肺损伤，而肺损伤在减少肺机械应力方面可能超过预期的保护作用[12]。

总之，关于在危重患者中使用异氟醚，首先要考虑的是权衡其作为催眠药的好处，至少在短期内是一种有吸引力的替代品。尽管与其他静脉安眠药相比，其对危重患者的长期影响和结果仍不清楚，但异氟醚似乎越来越多地用于 ICU。一些科学协会认为异氟醚是需要中度或深度镇静的通气患者的一线镇静剂，因为它的作用持续时间短且安全性高。但他们的建议强调了对 ICU 医护人员进行充分培训的重要性，以优化其管理并最大限度地降低相关风险 [13]。其他潜在的好处还有待证明。目前，正在需要镇静超过 48 小时的患者中进行异丙酚的比较研究，重点是谵妄或机械通气时间等结果。异氟醚可能减轻自主呼吸患者的压力和劳损或对肺和横膈膜有保护作用的可能性是一个非常有吸引力的假设，需要在重症监护环境中的临床试验中得到证实。

作者声明没有利益冲突。

在当前研究期间没有生成或分析数据集。

Müller-Wirtz LM、O'Gara B、Gama de Abreu M、Schultz MJ、Beitler JR、Jerath A 等人。用于肺和隔膜保护性镇静的挥发性麻醉剂。暴击护理。2024;28:269.

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文章 PubMed 谷歌学术
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孔特雷拉斯 S，吉梅内斯-埃斯帕扎 C，卡巴列罗 J;西班牙重症监护医学和冠状动脉病房协会（SEMICYUC）的镇静、镇痛和谵妄工作组（GTSAD）。危重患者吸入镇静的实用方法。Med Intensiva.2024;48:467–76

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作者和单位

西班牙马德里拉巴斯大学医院重症监护医学科 Paseo de La Castellana 261， 28046

何塞·曼努埃尔·阿尼翁和安多尼·加西亚-穆尼奥斯
西班牙马德里 IdiPAZ 拉巴斯大学医院研究所

何塞·曼努埃尔·阿尼翁和安多尼·加西亚-穆尼奥斯
西班牙马德里卡洛斯三世健康研究所呼吸疾病生物医学研究中心网络（CIBERES）

何塞·曼努埃尔·阿尼翁和费尔南多·苏亚雷斯-西普曼
西班牙马德里 Universitario La Princesa 医院重症监护医学科

费尔南多·苏亚雷斯-西普曼 & 阿里斯·佩雷斯-卢森多
西班牙马德里 Universitario Infanta Leonor 医院重症监护医学科
玛丽亚·帕斯·埃斯库埃拉

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贡献

JMA、FSS、MPE、APL 和 AGM 为最初的概念和设计做出了贡献。JMA 和 FSS 参与了手稿的最终起草。所有作者都阅读并批准了最终稿件。

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与何塞·曼努埃尔·阿尼翁（José Manuel Añón）的通信。

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