We appreciate the comment by Añón and colleagues on our review article, which contributes to the discussion of potential benefits of inhaled sedation beyond hypnosis [1]. One key purpose of review articles is to explore developing areas of research. As Añón and colleagues illustrate well in their comment, our article synthesizes established pharmacological properties of volatile anesthetics with early findings on their use in transitioning critically ill patients to spontaneous ventilation under inhaled sedation, aiming to evaluate potential lung and diaphragm protection benefits [2]. Our focus was on highlighting the importance of gathering detailed clinical data to explore feasibility of lung- and diaphragm-protective ventilation across various sedatives, including volatile anesthetics, rather than drawing any definitive conclusions.

We agree that an increase in instrumental dead space, especially in patients ventilated with lower tidal volumes, where it can add up to 15–30% to the dead space fraction, should be minimized. It is up to the industry to ensure that this consideration is incorporated into further developments.

Completely abolishing respiratory drive with sedation is easy—much easier than titrating sedation and ventilatory support for safe and sufficient spontaneous ventilation. On the one hand, volatile anesthetics provide a broad dose range in which respiratory drive is maintained and can thus be modulated. On the other hand, if return of spontaneous breathing efforts is not a treatment goal, spontaneous breathing activity can be suppressed under inhaled sedation with volatile anesthetics. This becomes apparent from comparing spontaneous ventilation time rates of the multi-center population of the Sedaconda trial with our single-center subgroup [3, 4]. With strongly enforced treatment standards that promote transition to spontaneous ventilation, patients sedated with isoflurane at our center were breathing spontaneously during 82% of time compared to only 42% of time at other centers within the first 20 h after randomization [3, 4].

To promote clarity, we advocate a tailored approach rather than a “one-sedative-fits-all” strategy. Beyond traditional sedation scales, it remains essential to consider how specific sedatives impact respiratory drive and effort to achieve individualized, patient-centered sedation. While inhaled sedation may not suit every patient or situation, it is a valuable addition to our sedation toolbox. Particularly, in patients who require moderate-to-deep sedation but at the same time should transition to spontaneous ventilation, inhaled sedation can be a game changer.

No datasets were generated or analysed during the current study.

1. Añón JM, Suarez-Sipmann F, Paz Escuela M, Perez-Lucendo A, García-Muñoz A. Volatile anaesthetics for ICU sedation: beyond hypnosis? Crit Care. 2024.

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

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3. Meiser A, Volk T, Wallenborn J, Guenther U, Becher T, Bracht H, et al. Inhaled isoflurane via the anaesthetic conserving device versus propofol for sedation of invasively ventilated patients in intensive care units in Germany and Slovenia: an open-label, phase 3, randomised controlled, non-inferiority trial. Lancet Respir Med. 2021;9:1231–40.

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4. Müller-Wirtz LM, Behne F, Kermad A, Wagenpfeil G, Schroeder M, Sessler DI, et al. Isoflurane promotes early spontaneous breathing in ventilated intensive care patients: a post hoc subgroup analysis of a randomized trial. Acta Anaesthesiol Scand. 2022;66:354–64.

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This manuscript was supported through the collaboration between LMM-W and MJS within the ESAIC mentorship program 2023 (ESAIC_MSP_2023_LM).

No funding was received related to this manuscript.

Authors and Affiliations

1. Department of Anesthesiology, Friedrich-Alexander-Universität Erlangen-Nürnberg, University Hospital Erlangen, 91054, Erlangen, Germany

   Lukas M. Müller-Wirtz

2. OUTCOMES RESEARCH CONSORTIUM, Houston, TX, USA

   Lukas M. Müller-Wirtz

3. Department of Intensive Care, Amsterdam University Medical Center, Amsterdam, The Netherlands

   Marcus J. Schultz

4. Division of Cardiac Thoracic Vascular Anesthesia and Intensive Care Medicine, Department of Anesthesiology, Intensive Care Medicine and Pain Medicine, Medical University of Vienna, Vienna, Austria

   Marcus J. Schultz

5. Department of Anesthesiology, Intensive Care and Pain Therapy, Saarland University Medical Center and Saarland University Faculty of Medicine, Homburg, Saarland, Germany

   Andreas Meiser

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Contributions

All authors contributed to conception and design of this manuscript, performed critical revisions for important intellectual content, and approved the final version before submission.

Corresponding author

Correspondence to Lukas M. Müller-Wirtz.

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Competing interests

Lukas M. Müller-Wirtz received travel expenses and honoraria for lectures from Sedana Medical (Danderyd, Sweden). Marcus J. Schultz reports no conflicts of interest related to the topic. Andreas Meiser received consulting fees from Sedana Medical, as well as travel expenses and honoraria for lectures from Sedana Medical.

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Müller-Wirtz, L.M., Schultz, M.J. & Meiser, A. Reply to “volatile anaesthetics for ICU sedation: beyond hypnosis?”: A comment on “volatile anesthetics for lung- and diaphragm-protective sedation”. Crit Care 28, 393 (2024). https://doi.org/10.1186/s13054-024-05182-w

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• Received: 14 November 2024

• Accepted: 18 November 2024

• Published: 28 November 2024

• DOI: https://doi.org/10.1186/s13054-024-05182-w

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我们感谢 Añón 及其同事对我们综述文章的评论，这有助于讨论吸入镇静在催眠之外的潜在益处 [1]。评论文章的一个关键目的是探索发展中的研究领域。正如 Añón 及其同事在他们的评论中很好地说明的那样，我们的文章综合了挥发性麻醉剂的既定药理学特性，以及它们在吸入镇静下将危重患者过渡到自主通气的早期发现，旨在评估潜在的肺和隔膜保护益处 [2]。我们的重点是强调收集详细临床数据的重要性，以探索在各种镇静剂（包括挥发性麻醉剂）中肺和隔膜保护性通气的可行性，而不是得出任何明确的结论。

我们同意，应尽量减少器械死腔的增加，尤其是在潮气量较低通气的患者中，死腔死腔分数会增加 15-30%。行业有责任确保将这一考虑纳入进一步的开发中。

通过镇静功能完全消除呼吸驱动很容易——比滴定镇静和通气支持实现安全和充足的自主通气要容易得多。一方面，挥发性麻醉剂提供了广泛的剂量范围，在该范围内可以维持呼吸驱动，因此可以进行调节。另一方面，如果恢复自主呼吸努力不是治疗目标，则可以在挥发性麻醉剂吸入镇静下抑制自主呼吸活动。通过将 Sedaconda 试验的多中心人群的自主通气时间率与我们的单中心亚组进行比较，这一点变得很明显 [3， 4]。由于严格执行的治疗标准促进了向自主通气的过渡，在我们中心使用异氟醚镇静的患者在 82% 的时间内自主呼吸，而其他中心在随机分组后的前 20 小时内只有 42% 的时间 [3， 4]。

为了提高清晰度，我们提倡量身定制的方法，而不是“一针一线镇静剂”策略。除了传统的镇静量表之外，仍然必须考虑特定镇静剂如何影响呼吸驱动和努力，以实现个体化、以患者为中心的镇静。虽然吸入镇静剂可能并不适合每个患者或情况，但它是我们镇静工具箱的宝贵补充。特别是，对于需要中度至深度镇静但同时应过渡到自主通气的患者，吸入镇静可以改变游戏规则。

在当前研究期间没有生成或分析数据集。

1. 
   Añón JM， Suarez-Sipmann F， Paz Escuela M， Perez-Lucendo A， García-Muñoz A. 用于 ICU 镇静的挥发性麻醉剂：超越催眠？暴击护理。2024.

2. 
   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.

   
   文章： PubMed PubMed Central Google Scholar

3. 
   Meiser A、Volk T、Wallenborn J、Guenther U、Becher T、Bracht H 等人。通过麻醉保存装置吸入异氟醚与异丙酚用于德国和斯洛文尼亚重症监护病房有创通气患者的镇静：一项开放标签、3 期、随机对照、非劣效性试验。柳叶刀呼吸医学 2021;9:1231–40.

   
   论文 CAS PubMed Google Scholar

4. 
   Müller-Wirtz LM、Behne F、Kermad A、Wagenpfeil G、Schroeder M、Sessler DI 等人。异氟醚促进通气重症监护患者的早期自主呼吸：一项随机试验的事后亚组分析。麻醉学报扫描 2022;66:354–64.

   
   文章 PubMed 谷歌学术

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   德国埃尔朗根大学医院 Friedrich-Alexander-Universität Erlangen-Nürnberg 麻醉学系，邮编 91054

    卢卡斯·穆勒-维尔茨

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   美国德克萨斯州休斯顿 OUTCOMES RESEARCH CONSORTIUM

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   荷兰阿姆斯特丹大学医学中心重症监护科

    马库斯·舒尔茨

4. 
   奥地利维也纳医科大学麻醉科、重症监护医学和疼痛医学科、麻醉学、胸腔血管麻醉和重症监护医学科

    马库斯·舒尔茨

5. 
   德国萨尔州洪堡市萨尔大学医学中心和萨尔大学医学院麻醉学、重症监护和疼痛治疗系

    安德烈亚斯·迈泽

1. 
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