Volatile anaesthetics for ICU sedation: beyond hypnosis?

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.

Competing Interests

The authors declare no competing interests.