Volatile anaesthetics for ICU sedation: beyond hypnosis?

Abstract

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.

1. 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.

   Article PubMed PubMed Central Google Scholar

2. Bourgeois T, Ringot M, Ramanantsoa N, Matrot B, Dauger S, Delclaux C, et al. Breathing under anaesthesia. Anesthesiology. 2019;130:995–1006.

   Article PubMed Google Scholar

3. Yang Y, Ou M, Liu J, Zhao W, Zhuoma L, Liang Y, et al. Volatile anaesthetics activate a leak sodium conductance in retrotrapezoid nucleus neurons to maintain breathing during anaesthesia in mice. Anesthesiology. 2020;133:824–38.

   Article CAS PubMed Google Scholar

4. Lazarenko RM, Fortuna MG, Shi Y, Mulkey DK, Takakura AC, Moreira TS, et al. Anaesthetic activation of central respiratory chemoreceptor neurons involves inhibition of a THIK-1-like background K+ current. J Neurosci. 2010;30:9324–34.

   Article CAS PubMed PubMed Central Google Scholar

5. Eikermann M, Malhotra A, Fassbender P, Zaremba S, Jordan AS, Gautam S, et al. Differential effects of isoflurane and propofol on upper airway dilator muscle activity and breathing. Anesthesiology. 2008;108:897–906.

   Article CAS PubMed Google Scholar

6. Hao X, Ou M, Li Y, Zhou C. Volatile anaesthetics maintain tidal volume and minute ventilation to a greater degree than propofol under spontaneous respiration. BMC Anesthesiol. 2021;21:238.

   Article CAS PubMed PubMed Central Google Scholar

7. Simons JCP, Pierce E, Diaz-Gil D, Malviya SA, Meyer MJ, Timm FP, et al. Effects of depth of propofol and sevoflurane anaesthesia on upper airway collapsibility, respiratory genioglossus activation, and breathing in healthy volunteers. Anesthesiology. 2016;125:525–34.

   Article CAS PubMed Google Scholar

8. van den Elsen MJ, Dahan A, Berkenbosch A, DeGoede J, van Kleef JW, Olievier ICW. Does subanaesthetic isoflurane affect the ventilatory response to acute isocapnic hypoxia in healthy volunteers? Anesthesiology. 1994;81:860–7.

   Article PubMed Google Scholar

9. van den Elsen M, Sarton E, Teppema L, Berkenbosch A, Dahan A. Influence of 0.1 minimum alveolar concentration of sevoflurane, desflurane and isoflurane on dynamic ventilatory response to hypercapnia in humans. Br J Anaesth. 1998;80:174–82.

   Article PubMed Google Scholar

10. Pandit JJ, Manning-Fox J, Dorrington KL, Robbins PA. Effects of subanaesthetic sevoflurane on ventilation. 2: response to acute and sustained hypoxia in humans. Br J Anaesth. 1999;83:210–6.

    Article CAS PubMed Google Scholar

11. Pandit JJ, Manning-Fox J, Dorrington KL, Robbins PA. Effects of subanaesthetic sevoflurane on ventilation. 1: response to acute and sustained hypercapnia in humans. Br J Anaesth. 1999;83:204–9.

    Article CAS PubMed Google Scholar

12. Lellouche F, Delorme M, Brochard L. Impact of respiratory rate and dead space in the current era of lung protective mechanical ventilation. Chest. 2020;158:45–7.

    Article PubMed Google Scholar

13. Contreras S, Giménez-Esparza C, Caballero J; Sedation, analgesia and Delirium Working Group (GTSAD) of the Spanish Society of Intensive and Critical Care Medicine and Coronary Units (SEMICYUC). Practical approach to inhaled sedation in the critically ill patient. Med Intensiva. 2024;48:467–76

Download references

Authors and Affiliations

1. Department of Intensive Care Medicine, Hospital Universitario La Paz, Paseo de La Castellana 261, 28046, Madrid, Spain

   José Manuel Añón & Andoni García-Muñoz

2. Instituto de Investigación del Hospital Universitario La Paz, IdiPAZ, Madrid, Spain

   José Manuel Añón & Andoni García-Muñoz

3. Centro de Investigación Biomédica en Red de Enfermedades Respiratorias (CIBERES), Instituto de Salud Carlos III, Madrid, Spain

   José Manuel Añón & Fernando Suarez-Sipmann

4. Department of Intensive Care Medicine, Hospital Universitario La Princesa, Madrid, Spain

   Fernando Suarez-Sipmann & Aris Perez-Lucendo

5. Department of Intensive Care Medicine , Hospital Universitario Infanta Leonor, Madrid, Spain

   María Paz Escuela

Authors

1. José Manuel AñónView author publications

   You can also search for this author in PubMed Google Scholar

2. Fernando Suarez-SipmannView author publications

   You can also search for this author in PubMed Google Scholar

3. María Paz EscuelaView author publications

   You can also search for this author in PubMed Google Scholar

4. Aris Perez-LucendoView author publications

   You can also search for this author in PubMed Google Scholar

5. Andoni García-MuñozView author publications

   You can also search for this author in PubMed Google Scholar

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.

Corresponding author

Correspondence to José Manuel Añón.

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-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/.

Reprints and permissions

Cite this article

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

Download citation

• Received: 02 November 2024

• Accepted: 06 November 2024

• Published: 15 November 2024

• DOI: https://doi.org/10.1186/s13054-024-05163-z

Share this article

Anyone you share the following link with will be able to read this content:

Get shareable link

Sorry, a shareable link is not currently available for this article.

Copy to clipboard

Provided by the Springer Nature SharedIt content-sharing initiative