Background: The Sedaconda Anesthetic Conserving Device (ACD-S) is used for inhaled sedation in intubated patients and has passive humidification properties linked to the carbon material. However, limited evaluations of the hygrometric performance are available. The main aim of the study was to assess the humidification performance of this device with different ventilator settings and ambient temperatures. Methods: We assessed hygrometry of inspiratory gases and resistance of the Sedaconda ACD-S using a bench test. Hygrometric measurements were performed with 5 min ventilations from 4.8 to 18 L/min (at constant ambient temperature: 25 ± 1°C) and with 3 ambient temperatures, 22-24°C, 25 ± 1°C, and 28-30°C (at constant minute ventilation: 10 L/min). Simulation of physiologic expiratory gases with an absolute humidity of 35 mg H2O/L was used for main measurements. Some measurements were made with expiratory humidity of 27.5 mg H2O/L which corresponds to what is found in patients with moderate hypothermia. Three hygrometric measurements using the psychrometric method were performed for each tested condition. Device resistance was evaluated before utilization and after 96 h on the humidified bench and compared with a paper- and foam-based heat and moisture exchangers (HME) with similar dead spaces. Results: In tested conditions, mean humidity output was 29.8 ± 1.3 mg H2O/L. We found slightly lower humidity output at low versus high minute ventilation (respectively 28.0 ± 0.3 vs 30.6 ± 0.3, P < .001) and lowest versus highest ambient temperature (29.6 ± 0.3 vs 31.0 ± 0.2 mg H2O/L, P = .02). These differences are probably not clinically important. We found a linear relationship between expiratory and inspiratory humidity (R2 = 0.98, P < .001). Resistance of the tested device was higher, in comparison with paper- and foam-based HMEs, and increased slightly after 96 h of use on the bench. Conclusions: The Sedaconda ACD-S is a high-performance passive humidifier device, within all tested conditions of minute ventilation, tidal volume, and ambient temperature. Resistance was slightly higher compared with HMEs with similar dead space and different materials.

Whether the use of inhaled or intravenous sedation affects outcomes differentially in mechanically ventilated adults with acute respiratory distress syndrome (ARDS) is unknown.

To determine the efficacy and safety of inhaled sevoflurane compared with intravenous propofol for sedation in patients with ARDS.

Phase 3 randomized, open-label, assessor-blinded clinical trial conducted from May 2020 to October 2023 with 90-day follow-up. Adults with early moderate to severe ARDS (defined by a ratio of Pao2 to the fraction of inspired oxygen of <150 mm Hg with a positive end-expiratory pressure of ≥8 cm H2O) were enrolled in 37 French intensive care units.

Patients were randomized to a strategy of inhaled sedation with sevoflurane (intervention group) or to a strategy of intravenous sedation with propofol (control group) for up to 7 days.

The primary end point was the number of ventilator-free days at 28 days; the key secondary end point was 90-day survival.

Of 687 patients enrolled (mean [SD] age, 65 [12] years; 30% female), 346 were randomized to sevoflurane and 341 to propofol. The median total duration of sedation was 7 days (IQR, 4 to 7) in both groups. The number of ventilator-free days through day 28 was 0.0 days (IQR, 0.0 to 11.9) in the sevoflurane group and 0.0 days (IQR, 0.0 to 18.7) in the propofol group (median difference, -2.1 [95% CI, -3.6 to -0.7]; standardized hazard ratio, 0.76 [95% CI, 0.50 to 0.97]). The 90-day survival rates were 47.1% and 55.7% in the sevoflurane and propofol groups, respectively (hazard ratio, 1.31 [95% CI, 1.05 to 1.62]). Among 4 secondary outcomes, sevoflurane was associated with higher 7-day mortality (19.4% vs 13.5%, respectively; relative risk, 1.44 [95% CI, 1.02 to 2.03]) and fewer intensive care unit-free days through day 28 (median, 0.0 [IQR, 0.0 to 6.0] vs 0.0 [IQR, 0.0 to 15.0]; median difference, -2.5 [95% CI, -3.7 to -1.4]) compared with propofol.

Among patients with moderate to severe ARDS, inhaled sedation with sevoflurane resulted in fewer ventilator-free days at day 28 and lower 90-day survival than sedation with propofol.

ClinicalTrials.gov Identifier: NCT04235608.

Background: Passive humidifiers, also known as heat-and-moisture exchangers (HMEs) are used to warm and humidify inspired gases delivered during mechanical ventilation. Recent data demonstrate that the evaluation and selection of these devices is not optimal, leading to severe complications, such as endotracheal tube occlusions. The aim of the study was to assess the humidification performances of a large number of commercially available devices, with the psychrometric method, and to compare the results with manufacturer's data. Methods: We assessed 113 devices using a bench test that simulated physiological ventilation conditions. Seventy-one devices were described by the manufacturers as HME without or with filtration properties (HMEF) and 42 as antimicrobial filters. Among the 71 HME/HMEF, 60% were foam-based, 32% were paper-based, 6% were fiber-based, and 1 had carbon media (HMEF with inhaled sedation function). Three hygrometric measurements using the psychrometric method for each device were performed after reaching a steady state and compared with manufacturers' data (based on the International Organization for Standardization [ISO] method). Results: Among the 71 HME/HMEF tested, only 24 (34%) delivered absolute humidity above 28 mg H2O/L. Nineteen percent of the foam-based and 57% of the paper-based HME/HMEF delivered desired levels of humidity. Humidification data provided by manufacturers were available for 59 HME/HMEFs. In all but one device, humidity output was overestimated using the ISO method. The median (interquartile) difference between our measurements and the manufacturers' data were 6.0 (3.8-8.7) mg H2O/L for devices described as HMEs (P < .001). Poor performing devices were detected only with the psychrometric method. Conclusions: Several HME/HMEFs performed poorly and should not be used for prolonged mechanical ventilation. The values determined by independent assessments were lower than values reported by manufacturers. Evaluation of a passive humidifier using the current ISO method does not guarantee provision of adequate humidification.

Patients undergoing invasive mechanical ventilation often require pharmacologic sedation to facilitate tolerance of this life-sustaining intervention, but sedatives currently used in routine care have substantial limitations. Isoflurane is an inhaled volatile anesthetic with pharmacologic properties potentially suitable to sedation of ventilator-dependent critically ill patients, but need for specialized drug administration equipment has limited its use historically to general anesthesia in the operating theatre. This trial will evaluate isoflurane, administered using a novel drug delivery system, for sedation of ventilator-dependent adult intensive care unit (ICU) patients in the United States (US).

The Inhaled Sedation versus Propofol in Respiratory Failure in the ICU (INSPiRE-ICU2) is a phase 3, multicenter, randomized, controlled, assessor-blinded non-inferiority trial that will evaluate efficacy and safety of inhaled isoflurane delivered via the Sedaconda ACD-S, compared to intravenous propofol, for sedation of mechanically ventilated adult ICU patients. At 16 US hospitals, 235 enrolled patients requiring continuous sedation during invasive mechanical ventilation will be randomized in 1.5:1 ratio to inhaled isoflurane or intravenous propofol for sedation. Treatment duration is expected to be at least 12 h and may last up to 48 (± 6) h or until no longer needing continuous sedation, whichever occurs first. The primary endpoint is the percentage of time sedation depth is maintained within the targeted range (Richmond Agitation Sedation Scale - 1 to - 4), in the absence of rescue sedation, during the treatment period. Secondary superiority outcomes include opioid exposure, wake-up time, cognitive recovery after end-of-treatment, and preservation of spontaneous breathing effort.

The INSPiRE-ICU2 trial will help determine the potential role of isoflurane for sedation of ventilator-dependent adult patients in the ICU. Key trial design features, including adoption of the estimand framework and blinded assessments of sedation depth, pain, and cognitive recovery, will ensure a rigorous evaluation of isoflurane for ICU sedation. TRIAL REGISTRATION: ClinicalTrials.gov, NCT05327296. First registered on April 5, 2022.

Volatile anesthetics are gaining attention as sedatives in intensive care units. Sedation is a significant risk factor for skeletal muscle atrophy and weakness in critically ill patients; however, volatile anesthetics' influence on skeletal muscle atrophy remains unclear. Therefore, we investigated their effects on skeletal muscle mass using a murine-derived muscle cell line and mice.

C2C12 myotubes were exposed to isoflurane or sevoflurane. Myotube diameter was assessed using immunofluorescence. The expression levels of Atrogin-1, MuRF1, and LC3-II and phosphorylation levels of p70 S6K and Akt were analyzed to evaluate protein degradation and synthesis. To determine whether these effects were mediated through the Akt pathway, experiments with insulin-like growth factor 1 (IGF-1) were performed. Furthermore, mice skeletal muscle exposed to isoflurane or sevoflurane were compared with control mice and short-term immobility mice induced by sciatic nerve denervation (DN) or hindlimb suspension (HS).

Exposure of C2C12 myotubes to 2.8% isoflurane or 5.0% sevoflurane reduced the myotube diameter by 14.4 µm (95% confidential interval [CI], 11.7-17.1, P < .001) and 13.2 µm (95% CI, 10.1-16.2, P < .001), respectively. Exposure to 2.8% isoflurane increased the expressions of Atrogin-1 (2.9-fold [95% CI, 2.1- to 3.8-fold], P < .001), MuRF1 (3.1-fold [95% CI, 2.4- to 3.8-fold], P < .001), and LC3-II (1.6-fold [95% CI, 1.4- to 1.8-fold], P < .001), whereas decreasing phosphorylation of p70 S6K (0.3-fold [95% CI, 0.2- to 0.4-fold], P < .001) and Akt (0.4-fold [95% CI, 0.3- to 0.5-fold], P < .001). Exposure to 5.0% sevoflurane resulted in similar effects. Additionally, IGF-1 counteracted the effects of isoflurane on myotube mass. In mice skeletal muscle, exposure to 1% isoflurane or 1.5% sevoflurane decreased Akt phosphorylation (isoflurane: 0.4-fold [95% CI, 0.1- to 0.8-fold], P = .003; sevoflurane: 0.5-fold [95% CI, 0.4- to 0.6-fold], P = .011) and increased the expression levels of Atrogin-1 (isoflurane: 4.1-fold [95% CI, 3.2- to 5.1-fold], P < .001; sevoflurane: 2.3-fold [95% CI, 1.1- to 3.5-fold], P = .026), MuRF1 (isoflurane: 2.7-fold [95% CI, 1.3- to 4.1-fold], P = .01; sevoflurane: 2.3-fold [95% CI, 1.0- to 3.7-fold], P = .022), and LC3-II (isoflurane: 1.9-fold [95% CI, 0.9- to 3.0-fold], P = .045; sevoflurane: 1.5-fold [95% CI, 1.4- to 1.6-fold], P < .001) while decreasing p70 S6K phosphorylation (isoflurane: 0.5-fold [95% CI, 0.4- to 0.6-fold], P = .013; sevoflurane: 0.7-fold [95% CI, 0.6- to 0.8-fold], P = .008) compared with DN. Similar results were observed when comparing between isoflurane or sevoflurane exposure and HS.

Volatile anesthetics induce skeletal muscle atrophy by downregulating the Akt pathway, suggesting they may exacerbate skeletal muscle atrophy beyond immobility effects.

Extracorporeal membrane oxygenation (ECMO) is an established technique for managing severe cardiorespiratory failure. However, it is invasive and requires profound analgo-sedation during initiation and often throughout the therapy. Managing sedation in venovenous (VV) ECMO patients is particularly challenging due to the impact of ECMO circuits on pharmacokinetics and specific patient requirements. This can lead to unpredictable sedative effects and require multiple drugs at higher doses. Additionally, sedation is usually managed with traditional scoring methods, which are subjective and invalid during neuromuscular blockade. These uncertainties may impact outcomes. Recent clinical practice increasingly focuses on reducing sedation to enable earlier physiotherapy and mobilisation, particularly in patients awaiting transplants or receiving mechanical circulatory support. In this context, processed electroencephalogram-based (pEEG) sedation monitoring might be promising, having shown benefits in general anaesthesia and intensive care. However, the technology has limitations, and its benefits in ECMO practice have yet to be formally evaluated. This review provides insights into the challenges of ECMO sedation, including pharmacokinetics, unique ECMO requirements, and the implications of inadequate sedation scores. Finally, it includes a brief overview of the practicality and limitations of pEEG monitoring during VV-ECMO, highlighting a significant research gap.

Background: Inhaled sedation is increasing in ICUs, with active carbon filters (ACFs) commonly used for evacuating halogenated gases. However, the potential benefits of a waste anesthetic gas system (WAGS) similar to the ones used in operating rooms should be explored. To limit the suction over the flow sensor where the WAGS is connected on ICU ventilators, an anesthetic gas receiving system (AGRS) is required, constituting with the WAGS an active gas receiving and scavenging system (AGRSS). Ensuring that this whole device does not compromise the flow sensor reliability is crucial. The aim of this study was to compare various gas evacuation devices and assess the reliability of AGRSS on ICU ventilators. Methods: In this experimental study, pressures and flows were recorded during the ventilation of a test lung using various ventilator settings and gas evacuation methods: no device (reference condition), ACF, the WAGS alone, AGRSS (WAGS and AGRS together), and the expiratory valve connected to the medical vacuum system with the AGRS in between. Visual comparisons of the pressure and flow curves followed by a statistical analysis comparing median pressures and flows of each device to the reference were performed. Results: The test lung model demonstrated consistent comparability in pressures and flows among all devices, except for the WAGS alone, which exhibited discordance through significant overestimation or underestimation. Conclusions: These findings indicate that using a WAGS with the AGRS system appeared to be reliable for managing gas evacuation in ICUs without compromising pressure or flow delivery. The data from this experimental trial should be confirmed with clinical studies involving human subjects. Given the increasing use of inhaled sedation in ICUs, these results support the daily application of the WAGS with the AGRS for gas evacuation, similar to its established use in anesthesiology.

Background: Severe strokes often require deep sedation, yet the optimal sedation regimen remains unclear. This comparative study compared the efficacy of achieving target sedation depth using inhaled (isoflurane) versus intravenous (propofol) sedation. Methods: This prospective, observational, proof-of-concept study was conducted between July 2022 and June 2023 at two University Hospitals with dedicated neurological intensive care units. We included conservatively treated patients with severe space-occupying strokes (ischemic or haemorrhagic) requiring deep sedation. Patients received either inhaled or intravenous sedation. Sedation targets were defined in the morning rounds using the Richmond-Agitation-Sedation-Scale and were assessed at two subsequent time points (7 p.m. and 7 a.m.) during hospital stay. The primary outcome was the number of days where the predefined sedation target was achieved at both time points, comparing between the two sedation regimens. Secondary and safety outcomes included the incidence of delirium, pneumonia, functional outcomes, mortality, and vasopressor doses. Results: Seventy-nine patients (age 71 [63-81] years, 31 female) were included. Patients sedated with isoflurane achieved the sedation target significantly more often, with 182/444 (41%) compared to 80/497 (16%) assessments in patients sedated with propofol (RR 1.4; 95%-CI: 1.3-1.6). This effect was consistent across all sedation stages, specifically in the deep sedation targets (RR 1.5; 95%-CI: 1.2-1.9) and no-sedation target (RR 5.1; 95%-CI: 2.8-9.4). Secondary and safety outcomes revealed no significant differences. Conclusions: Isoflurane sedation offers a benefit for invasively ventilated stroke patients with respect to sedation targets. Specifically, isoflurane facilitates faster awakening when transitioning from deep sedation to awakening. These data encourage further confirmatory studies for specific stroke-patient groups.

Inhaled sedation uses halogenated drugs (isoflurane and sevoflurane) in a liquid state that, through a vaporizer, change to a gaseous state and reach the patient by the respiratory route. These drugs have a rapid onset of action, with minimal metabolism and elimination takes place almost exclusively through the airways. They do not cause significant tolerance, tachyphylaxis or significant abstinence. Inhaled sedation enables a rapid and more predictable awakening and reduced the need for opioids and neuromuscular relaxants (than intravenous sedation). In addition, have bronchodilatory, anticonvulsing and potential antiinflammatory and cardioprotective effects. To date, inhaled sedation has been practically exclusive to the areas of anesthesia and surgery. For its therapeutic application in the environment of the Intensive Care Units (ICU) there are two devices, Sedaconda ACD® and Mirus®. Its design, adaptable to different respirators and with a safe scavenging gas system, has facilitated its introduction in the ICUs. Scientific evidence supports the use of isoflurano and Sevoflurano (with limitations), especially in cases of moderate-deep sedation, and for people with acute respiratory distress syndrome, acute bronchospasm, status epilepticus, people who are difficult to sedate, prolonged sedation (only isoflurano) and patients post cardiac arrest or who need daily neurological assessment. Halogenated sedation is safe and effective for the critical patient undergoing mechanical ventilation. However, it is not exempt from risks and requires learning by professionals who will prescribe and/or apply. Nurses must know the characteristics of the drug, its handling, and be an expert in the route of administration so that the therapy is safe for the patient and health professionals.

Advances in our approach to treating pain and sedation when caring for patients in the intensive care unit (ICU) have been propelled by decades of robust trial data, knowledge gained from patient experiences, and our evolving understanding of how pain and sedation strategies affect patient survival and long term outcomes. These data contribute to current practice guidelines prioritizing analgesia-first sedation strategies (analgosedation) that target light sedation when possible, use of short acting sedatives, and avoidance of benzodiazepines. Together, these strategies allow the patient to be more awake and able to participate in early mobilization and family interactions. The covid-19 pandemic introduced unique challenges in the ICU that affected delivery of best practices and patient outcomes. Compliance with best practices has not returned to pre-covid levels. After emerging from the pandemic and refocusing our attention on optimal pain and sedation management in the ICU, it is imperative to revisit the data that contributed to our current recommendations, review the importance of best practices on patient outcomes, and consider new strategies when advancing patient care.

Acute respiratory distress syndrome (ARDS) presents significant challenges in critical care, primarily due to its inflammatory nature, which leads to impaired gas exchange and respiratory mechanics. While mechanical ventilation (MV) is essential for patient support, the transition from controlled to assisted ventilation is complex and may be associated with intensive care unit-acquired weakness, ventilator-induced diaphragmatic dysfunction and patient self-inflicted lung injury. This paper explores the multifaceted challenges encountered during this transition, with a focus on respiratory effort, sedation management, and monitoring techniques, and investigates innovative approaches to enhance patient outcomes. The key strategies include optimizing sedation protocols, employing advanced monitoring methods like esophageal pressure measurements, and implementing partial neuromuscular blockade to prevent excessive respiratory effort. We also emphasize the importance of personalized treatment plans and the integration of artificial intelligence to facilitate timely transitions. By highlighting early rehabilitation techniques, continuously assessing the respiratory drive, and fostering collaboration among multidisciplinary teams, clinicians can improve the transition from controlled to assisted MV, ultimately enhancing recovery and long-term respiratory health in patients with ARDS.

A narrative expert review aiming to summarize the clinical epidemiology and management of critically ill patients with malignant hyperthermia (MH).

Medline searches were conducted to identify relevant articles describing the epidemiology, pathophysiology, and management of MH. Guidelines from key MH organizations were also incorporated into this review.

Relevant studies regarding MH in both ICU and perioperative settings were reviewed.

Data from relevant studies were summarized and qualitatively assessed.

MH is a severe reaction triggered by inhalational volatile anesthetics and succinylcholine in genetically susceptible patients. The condition is characterized by an early onset (min to hr) rise in temperature, hypercarbia, and muscular rigidity following exposure to triggering medications with potential complications of coagulopathy, rhabdomyolysis, and acute kidney injury. Acute management necessitates a coordinated multidisciplinary team approach with specific management using dantrolene, active cooling, and hyperventilation. A suspected MH reaction has important implications for future anesthetic exposure for both the patient and their family. All suspected reactions should be followed up at a specialized MH testing center using muscle contracture and genetic testing.

Increasing use of inhalational anesthetics in the ICU underscores the need for enhanced education on the diagnosis and management of MH to ensure optimal patient sedation care and safety.

Intensive care unit (ICU) patients receive highly complex care and often require sedation as part of their management. ICU sedation has traditionally been delivered using intravenous (IV) agents due to the impractical use of anaesthetic machines in this setting, which are used to deliver volatile sedation. Sedaconda anaesthetic conserving device (ACD)-S (previously known as AnaConDa-S) is a device which allows for the delivery of volatile sedation via the majority of mechanical ventilators by being inserted in the breathing circuit where the heat and moisture exchanger is normally placed. The National Institute of Health and Care Excellence (NICE), as part of the Medical Technologies Evaluation Programme, considered the potential benefits of using Sedaconda ACD-S compared to standard IV sedation in ICU patients. Here we describe the evidence evaluation undertaken by NICE on this technology, supported by CEDAR. CEDAR considered the evidence present in 21 publications that compared the clinical outcomes of patients receiving Sedaconda ACD-S-delivered sedation and IV sedation, and critiqued the economic model provided by the manufacturer. Clinical expert input during the evaluation process was used extensively to ensure that the relevant clinical evidence was captured and that the economic model was suitable for the UK setting. Due to the uncertainty of the evidence, sensitivity analysis was carried out on the key economic inputs to ensure the reliability of the results. Economic modelling has shown that Sedaconda ACD-S-delivered isoflurane sedation is cost saving on a 30-day horizon compared to IV sedation by £3833.76 per adult patient and by £2837.41 per paediatric patient. Clinical evidence indicated that Sedaconda ACD-S-delivered isoflurane sedation is associated with faster patient wake-up times than standard of care. Consequently, NICE recommended Sedaconda ACD-S as an option for delivering sedation in the ICU setting, but noted that further research should inform whether Sedaconda ACD-S-delivered sedation is of benefit to any particular subgroup of patients.

Sedation in mechanically ventilated adults in the intensive care unit (ICU) is commonly achieved with intravenous infusions of propofol, dexmedetomidine or benzodiazepines. Significant limitations associated with each can impact their usage. Inhaled isoflurane has potential benefit for ICU sedation due to its safety record, sedation profile, lack of metabolism and accumulation, and fast wake-up time. Administration in the ICU has historically been restricted by the lack of a safe and effective delivery system for the ICU. The Sedaconda Anaesthetic Conserving Device-S (Sedaconda ACD-S) has enabled the delivery of inhaled volatile anaesthetics for sedation with standard ICU ventilators, but it has not yet been rigorously evaluated in the USA. We aim to evaluate the efficacy and safety of inhaled isoflurane delivered via the Sedaconda ACD-S compared with intravenous propofol for sedation of mechanically ventilated ICU adults in USA hospitals.

INhaled Sedation versus Propofol in REspiratory failure in the ICU (INSPiRE-ICU1) is a phase 3, multicentre, randomised, controlled, open-label, assessor-blinded trial that aims to enrol 235 critically ill adults in 14 hospitals across the USA. Eligible patients are randomised in a 1.5:1 ratio for a treatment duration of up to 48 (±6) hours or extubation, whichever occurs first, with primary follow-up period of 30 days and additional follow-up to 6 months. Primary outcome is percentage of time at target sedation range. Key secondary outcomes include use of opioids during treatment, spontaneous breathing efforts during treatment, wake-up time at end of treatment and cognitive recovery after treatment.

Trial protocol has been approved by US Food and Drug Administration (FDA) and central (Advarra SSU00208265) or local institutional review boards ((IRB), Cleveland Clinic IRB FWA 00005367, Tufts HS IRB 20221969, Houston Methodist IRB PRO00035247, Mayo Clinic IRB Mod22-001084-08, University of Chicago IRB21-1917-AM011 and Intermountain IRB 033175). Results will be presented at scientific conferences, submitted for publication, and provided to the FDA.

NCT05312385.

Poor neurological outcome is common following a cardiac arrest. The use of volatile anesthetic agents has been proposed during post-resuscitation to improve outcome.

To determine the effects of inhaled isoflurane on neurological outcome, delirium incidence, ICU length-of-stay, ventilation duration, mortality during post-resuscitation care of ICU patients.

510 patients were admitted within our medical ICU following a cardiac arrest during the study period, 401 of them being sedated using intravenous sedation prior to 2017 and 109 of them using inhaled isoflurane according to a standardized protocol following 2017.

Matched-pair analysis depicted a delirium incidence decrease, without improved neurologic outcome on ICU discharge (CPC ≤ 2) for isoflurane patients (16.1% vs 32.2%, p 0.03 and 29% vs 23%, p 0.47, respectively). Ventilation duration and ICU length of stay were shorter for isoflurane patients (78 vs 167 h, p 0.01 and 7.9 vs 8.5 days, p 0.01 respectively). Isoflurane had no impact on mortality.

In this propensity-matched control study, isoflurane sedation during the post-resuscitation care of ICU patients was associated with a lower incidence of delirium, a shorter duration of mechanical ventilation and a reduced ICU length of stay. Prospective data are needed before its widespread use.

This review explores the complex interactions between sedation and invasive ventilation and examines the potential of volatile anesthetics for lung- and diaphragm-protective sedation. In the early stages of invasive ventilation, many critically ill patients experience insufficient respiratory drive and effort, leading to compromised diaphragm function. Compared with common intravenous agents, inhaled sedation with volatile anesthetics better preserves respiratory drive, potentially helping to maintain diaphragm function during prolonged periods of invasive ventilation. In turn, higher concentrations of volatile anesthetics reduce the size of spontaneously generated tidal volumes, potentially reducing lung stress and strain and with that the risk of self-inflicted lung injury. Taken together, inhaled sedation may allow titration of respiratory drive to maintain inspiratory efforts within lung- and diaphragm-protective ranges. Particularly in patients who are expected to require prolonged invasive ventilation, in whom the restoration of adequate but safe inspiratory effort is crucial for successful weaning, inhaled sedation represents an attractive option for lung- and diaphragm-protective sedation. A technical limitation is ventilatory dead space introduced by volatile anesthetic reflectors, although this impact is minimal and comparable to ventilation with heat and moisture exchangers. Further studies are imperative for a comprehensive understanding of the specific effects of inhaled sedation on respiratory drive and effort and, ultimately, how this translates into patient-centered outcomes in critically ill patients.

The use of sedatives in Intensive Care Units (ICU) is essential for relieving anxiety and stress in mechanically ventilated patients, and it is related to clinical outcomes, duration of mechanical ventilation, and length of stay in the ICU. Inhaled sedatives offer benefits such as faster awakening and extubation, decreased total opioid and neuromuscular blocking agents (NMB) doses, as well as bronchodilator, anticonvulsant, and cardiopulmonary and neurological protective effects. Inhaled sedation is administered using a specific vaporizer. Isoflurane is the recommended agent due to its efficacy and safety profile. Inhaled sedation is recommended for moderate and deep sedation, prolonged sedation, difficult sedation, patients with acute respiratory distress syndrome (ARDS), status asthmaticus, and super-refractory status epilepticus. By offering these significant advantages, the use of inhaled sedatives allows for a personalized and controlled approach to optimize sedation in the ICU.

There are many common malignant tumors in clinic. Among them, lung cancer is caused by the failure of suction system, which seriously threatens the life safety of patients. Recent studies have found that anesthetics have achieved certain efficacy in many cancers. Isoflurane, an inhaled anesthetic, is used in this study to explore whether it can prevent the lung cancer development. The A549 and H1299 were purchased. Cell viability was tested by CCK-8 experiment. Cell death and pyroptosis were analyzed by PI staining as well as flow cytometry. HMGB1 as well as RAGE protein levels were tested by Western blot. The same is true of pyroxin-related proteins. The HMGB1 as well as RAGE levels in the lung cancer tissues were determined by Western blot along with immunohistochemistry. Isoflurane treatment can reduce cell viability and promote cell pyroptosis. Additionally, the protein levels of cleaved caspase-1, IL-1β, GSDMD-N, NLRP3, HMGB1, and RAGE were dramatically up-regulated in the lung cancer after isoflurane treatment. Down-regulated proteins in lung cancer tissues include HMGB1 and RAGE proteins. After HMGB1 knockdown or FPS-ZM1 treatment, the role of isoflurane in the lung cancer was neutralized. This study demonstrated that isoflurane induced the cell pyroptosis in the lung cancer through activating the HMGB1/RAGE pathway.

The objective was to compare sevoflurane, a volatile sedation agent with potential bronchodilatory properties, with propofol on respiratory mechanics in critically ill patients with COPD exacerbation.

Prospective study in an ICU enrolling critically ill intubated patients with severe COPD exacerbation and comparing propofol and sevoflurane after 1:1 randomisation. Respiratory system mechanics (airway resistance, PEEPi, trapped volume, ventilatory ratio and respiratory system compliance), gas exchange, vitals, safety and outcome were measured at inclusion and then until H48. Total airway resistance change from baseline to H48 in both sevoflurane and propofol groups was the main endpoint.

Sixteen patients were enrolled and were sedated for 126 h(61-228) in the propofol group and 207 h(171-216) in the sevoflurane group. At baseline, airway resistance was 21.6cmH2O/l/s(19.8-21.6) in the propofol group and 20.4cmH2O/l/s(18.6-26.4) in the sevoflurane group, (p = 0.73); trapped volume was 260 ml(176-290) in the propofol group and 73 ml(35-126) in the sevoflurane group, p = 0.02. Intrinsic PEEP was 1.5cmH2O(1-3) in both groups after external PEEP optimization. There was neither early (H4) or late (H48) significant difference in airway resistance and respiratory mechanics parameters between the two groups.

In critically ill patients intubated with COPD exacerbation, there was no significant difference in respiratory mechanics between sevoflurane and propofol from inclusion to H4 and H48.

Sleep disruption is a common occurrence during medical care and is detrimental to patient recovery. Long-term sedation in the critical care setting is a modifiable factor that affects sleep, but the impact of different sedative-hypnotics on sleep homeostasis is not clear.

We conducted a systematic comparison of the effects of prolonged sedation (8 h) with i.v. and inhalational agents on sleep homeostasis. Adult Sprague-Dawley rats (n=10) received dexmedetomidine or midazolam on separate days. Another group (n=9) received propofol or sevoflurane on separate days. A third group (n=12) received coadministration of dexmedetomidine and sevoflurane. Wakefulness (wake), slow-wave sleep (SWS), and rapid eye movement (REM) sleep were quantified during the 48-h post-sedation period, during which we also assessed wake-associated neural dynamics using two electroencephalographic measures: theta-high gamma phase-amplitude coupling and high gamma weighted phase-lag index.

Dexmedetomidine-, midazolam-, or propofol-induced sedation increased wake and decreased SWS and REM sleep (P<0.0001) during the 48-h post-sedation period. Sevoflurane produced no change in SWS, decreased wake for 3 h, and increased REM sleep for 6 h (P<0.02) post-sedation. Coadministration of dexmedetomidine and sevoflurane induced no change in wake (P>0.05), increased SWS for 3 h, and decreased REM sleep for 9 h (P<0.02) post-sedation. Dexmedetomidine, midazolam, and coadministration of dexmedetomidine with sevoflurane reduced wake-associated phase-amplitude coupling (P≤0.01). All sedatives except sevoflurane decreased wake-associated high gamma weighted phase-lag index (P<0.01).

In contrast to i.v. drugs, prolonged sevoflurane sedation produced minimal changes in sleep homeostasis and neural dynamics. Further studies are warranted to assess inhalational agents for long-term sedation and sleep homeostasis.

Inhaled sedation of intensive care unit (ICU) patients ventilated >24 hours may have long term effects. We hypothesized that isoflurane has a better neuropsychological outcome in a one-year follow-up compared to propofol sedation.

All 66 patients included by the coordinating center of the ISOCONDA study (EudraCT#: 2016-004551-67) took part in this substudy (DRKS00020240). A delirium test (CAM-ICU) was performed 24 hours after end of sedation. Sedation-, ventilator-, ICU- and delirium-free days within 30 days were calculated. Patients were sent five questionnaires one, three and twelve months after ICU discharge: ICU-Memory-tool (ICU-MT), Short-Form-36-Health-survey (SF-36), Posttraumatic-Stress-Scale-14 (PTSS-14), WHO-Five-Well-Being-Index (WHO-5) and Hospital-Anxiety-Depression-Scale (HADS).

CAM-ICU was positive in 17% of patients, however 68% showed signs of delirium during the ICU stay (no group differences). Mortality was lower after isoflurane (30-days: 1/33 versus 7/33, P=0.024; One-year: 9/33 versus 14/33, P=0.156). Isoflurane led to significantly more sedation- (median [IQR]: 28[25-29] versus 24[21-29], P=0.016), ventilator- (28[24-29] versus 22[4-28], P=0.011), ICU- (23[13-26] versus 11[0-25], P=0.044) and delirium-free days (25[21-29] versus 20[12-28], P=0.031). Return rate of questionnaires was high (87/128). In the ICU-MT, isoflurane patients recalled significantly more factual memories after one year. Generally, the psychological tests suggested a poor quality of life (SF-36), high rates of post-traumatic-stress-disorder (PTSS-14: 38%) and depression (WHO-5: 54%, HADS: 43%), without significant group differences.

Isoflurane sedation leads to more delirium free days during the ICU treatment and more factual memories of the ICU stay one year after the ICU stay. However long-term outcome of ventilated ICU patients is poor, and there were no differences between isoflurane and propofol sedation.

This study aimed to explore the effects of sedative doses of propofol and isoflurane on microcirculation in septic mice compared to controls. Isoflurane, known for its potential as a sedation drug in bedside applications, lacks clarity regarding its impact on the microcirculation system. The hypothesis was that propofol would exert a more pronounced influence on the microvascular flow index, particularly amplified in septic conditions.

Randomized study was conducted from December 2020 to October 2021 involved 60 BALB/c mice, with 52 mice analyzed. Dorsal skinfold chambers were implanted, followed by intraperitoneal injections of either sterile 0.9 % saline or lipopolysaccharide for the control and sepsis groups, respectively. Both groups received propofol or isoflurane treatment for 120 min. Microcirculatory parameters were obtained via incident dark-field microscopy videos, along with the mean blood pressure and heart rate at three time points: before sedation (T0), 30 min after sedation (T30), and 120 min after sedation (T120). Endothelial glycocalyx thickness and syndecan-1 concentration were also analyzed.

In healthy controls, both anesthetics reduced blood pressure. However, propofol maintained microvascular flow, differing significantly from isoflurane at T120 (propofol, 2.8 ± 0.3 vs. isoflurane, 1.6 ± 0.9; P < 0.001). In the sepsis group, a similar pattern occurred at T120 without statistical significance (propofol, 1.8 ± 1.1 vs. isoflurane, 1.2 ± 0.7; P = 0.023). Syndecan-1 levels did not differ between agents, but glycocalyx thickness index was significantly lower in the isoflurane-sepsis group than propofol (P = 0.001).

Propofol potentially offers protective action against microvascular flow deterioration compared to isoflurane, observed in control mice. Furthermore, a lower degree of sepsis-induced glycocalyx degradation was evident with propofol compared to isoflurane.

Liver function of intensive care patients is routinely monitored by static blood pathology. For specific indications, liver specific cytochrome activity may be measured by the commercially available maximum liver function capacity (LiMAx) test via quantification of the cytochrome P450 1A2 (CYP1A2) dependent C-methacetin metabolism. Sedation with the volatile anesthetic isoflurane was suspected to abrogate the correlation of LiMAx test with global liver function. We hypothesized that isoflurane has a CYP1A2-activity and LiMAx test result decreasing effect.

In this monocentric, observational clinical study previously liver healthy intensive care patients, scheduled to be changed from propofol to isoflurane sedation, were enrolled. LiMAx testing was done before, during and after termination of isoflurane sedation.

The mean LiMAx value decreased during isoflurane sedation. Septic patients (n = 11) exhibited lower LiMAx values compared to non-septic patients (n = 11) at all time points. LiMAx values decreased with isoflurane from 140 ± 82 to 30 ± 34 µg kg-1 h-1 in the septic group and from 253 ± 92 to 147 ± 131 µg kg-1 h-1 in the non-septic group while laboratory markers did not imply significant hepatic impairment. Lactate increased during isoflurane inhalation without clinical consequence.

Sepsis and isoflurane have independently demonstrated an effect on reducing the hepatic CYP1A2-activity. A network model was constructed that could explain the mechanism through the influence of isoflurane on hypoxia inducible factor (HIF-1α) by upregulation of the hypoxia-inducible pathway and the downregulation of CYP1A2-activity via the ligand-inducible pathway. Thus, the increased anaerobic metabolism may result in lactate accumulation. The influence of isoflurane sedation on the validated correlation of global liver function with CYP1A2-activity measured by LiMAx testing needs to be investigated in more detail.

The discovery and utilization of volatile anesthetics has significantly transformed surgical practices since their inception in the mid-19th century. Recently, a paradigm shift is observed as volatile anesthetics extend beyond traditional confines of the operating theatres, finding diverse applications in intensive care settings. In the dynamic landscape of intensive care, volatile anesthetics emerge as a promising avenue for addressing complex sedation requirements, managing refractory lung pathologies including acute respiratory distress syndrome and status asthmaticus, conditions of high sedative requirements including burns, high opioid or alcohol use and neurological conditions such as status epilepticus. Volatile anesthetics can be administered through either inhaled route via anesthetic machines/devices or through extracorporeal membrane oxygenation circuitry, providing intensivists with multiple options to tailor therapy. Furthermore, their unique pharmacokinetic profiles render them titratable and empower clinicians to individualize management with heightened accuracy, mitigating risks associated with conventional sedation modalities. Despite the amounting enthusiasm for the use of these therapies, barriers to widespread utilization include expanding equipment availability, staff familiarity and training of safe use. This article delves into the realm of applying inhaled volatile anesthetics in the intensive care unit through discussing their pharmacology, administration considerations in intensive care settings, complication considerations, and listing indications and evidence of the use of volatile anesthetics in the critically ill patient population.

Sedation is used in intensive care units (ICU) to improve comfort and tolerance during mechanical ventilation, invasive interventions, and nursing care. In recent years, the use of inhalation anaesthetics for this purpose has increased. Our objective was to obtain and summarise the best evidence on inhaled sedation in adult patients in the ICU, and use this to help physicians choose the most appropriate approach in terms of the impact of sedation on clinical outcomes and the risk-benefit of the chosen strategy.

Given the overall lack of literature and scientific evidence on various aspects of inhaled sedation in the ICU, we decided to use a Delphi method to achieve consensus among a group of 17 expert panellists. The processes was conducted over a 12-month period between 2022 and 2023, and followed the recommendations of the CREDES guidelines.

The results of the Delphi survey form the basis of these 39 recommendations - 23 with a strong consensus and 15 with a weak consensus.

The use of inhaled sedation in the ICU is a reliable and appropriate option in a wide variety of clinical scenarios. However, there are numerous aspects of the technique that require further study.

Inhaled volatile anesthetics support management of status asthmaticus (SA), status epilepticus (SE), and difficult sedation (DS). This study aimed to evaluate the effectiveness, safety, and feasibility of using inhaled anesthetics for SA, SE, and DS in adult ICU and PICU patients.

MEDLINE, Cochrane Central Register of Controlled Trials, and Embase.

Primary literature search that reported the use of inhaled anesthetics in ventilated patients with SA, SE, and DS from 1970 to 2021.

Study data points were extracted by two authors independently. Quality assessment was performed using the Joanna Briggs Institute appraisal tool for case studies/series, Newcastle criteria for cohort/case-control studies, and risk-of-bias framework for clinical trials.

Primary outcome was volatile efficacy in improving predefined clinical or physiologic endpoints. Secondary outcomes were adverse events and delivery logistics. From 4281 screened studies, the number of included studies/patients across diagnoses and patient groups were: SA (adult: 38/121, pediatric: 28/142), SE (adult: 18/37, pediatric: 5/10), and DS (adult: 21/355, pediatric: 10/90). Quality of evidence was low, consisting mainly of case reports and series. Clinical and physiologic improvement was seen within 1-2 hours of initiating volatiles, with variable efficacy across diagnoses and patient groups: SA (adult: 89-95%, pediatric: 80-97%), SE (adults: 54-100%, pediatric: 60-100%), and DS (adults: 60-90%, pediatric: 62-90%). Most common adverse events were cardiovascular, that is, hypotension and arrhythmias. Inhaled sedatives were commonly delivered using anesthesia machines for SA/SE and miniature vaporizers for DS. Few (10%) of studies reported required non-ICU personnel, and only 16% had ICU volatile delivery protocol.

Volatile anesthetics may provide effective treatment in patients with SA, SE, and DS scenarios but the quality of evidence is low. Higher-quality powered prospective studies of the efficacy and safety of using volatile anesthetics to manage SA, SE, and DS patients are required. Education regarding inhaled anesthetics and the protocolization of their use is needed.

Inhaled sedation during invasive mechanical ventilation in patients with acute respiratory distress syndrome (ARDS) has received increasing attention. However, inhaled sedation devices increase dead-space ventilation and an undesirable effect is the increase in minute ventilation needed to maintain CO2 removal. A consequence of raising minute ventilation is an increase in mechanical power (MP) that can promote lung injury. However, the effect of inhaled sedation devices on MP remains unknown.

We conducted a bench study to assess and compare the effects of three devices delivering inhaled sevoflurane currently available in ICU (AnaConDa-50 mL (ANA-50), AnaConDa-100 mL (ANA-100), and MIRUS) on MP by using a test lung model set with three compliances (20, 40, and 60 mL/cmH2O). We simulated lung-protective ventilation using a low tidal volume and two levels of positive end-expiratory pressure (5 and 15 cmH2O) under ambient temperature and dry conditions. Following the insertion of the devices, either the respiratory rate or tidal volume was increased in 15%-steps until end-tidal CO2 (EtCO2) returned to the baseline value. MP was calculated at baseline and after EtCO2 correction using a simplified equation.

Following device insertion, the EtCO2 increase was significantly greater with MIRUS (+ 78 ± 13%) and ANA-100 (+ 100 ± 11%) than with ANA-50 (+ 49 ± 7%). After normalizing EtCO2 by adjusting minute ventilation, MP significantly increased by more than 50% with all inhaled sedation devices compared to controls. The lowest increase in MP was observed with ANA-50 (p < 0.05 versus ANA-100 and MIRUS). The Costa index, another parameter assessing the mechanical energy delivered to the lungs, calculated as driving pressure × 4 + respiratory rate, significantly increased by more than 20% in all experimental conditions. Additional experiments performed under body temperature, ambient pressure, and gas saturated with water vapor conditions, confirmed the main results with an increase in MP > 50% with all devices after normalizing EtCO2 by adjusting minute ventilation.

Inhaled sedation devices substantially increased MP in this bench model of protective ventilation, which might limit their benefits in ARDS.

To compare ICU-free (ICU-FD) and ventilator-free days (VFD) in the 30 days after randomization in patients that received isoflurane or propofol without receiving the other sedative.

A recent randomized controlled trial (RCT) compared inhaled isoflurane via the Sedaconda® anaesthetic conserving device (ACD) with intravenous propofol for up to 54 h (Meiser et al. 2021). After end of study treatment, continued sedation was locally determined. Patients were eligible for this post-hoc analysis only if they had available 30-day follow-up data and never converted to the other drug in the 30 days from randomization. Data on ventilator use, ICU stay, concomitant sedative use, renal replacement therapy (RRT) and mortality were collected.

Sixty-nine of 150 patients randomized to isoflurane and 109 of 151 patients randomized to propofol were eligible. After adjusting for potential confounders, the isoflurane group had more ICU-FD than the propofol group (17.3 vs 13.8 days, p = 0.028). VFD for the isoflurane and propofol groups were 19.8 and 18.5 respectively (p = 0.454). Other sedatives were used more frequently (p < 0.0001) and RRT started in a greater proportion of patients in the propofol group (p = 0.011).

Isoflurane via the ACD was not associated with more VFD but with more ICU-FD and less concomitant sedative use.

This article looks at the challenges of sedoanalgesia for sepsis patients, and argues for a personalised approach. Sedation is a necessary part of treatment for patients in intensive care to reduce stress and anxiety and improve long-term prognoses. Sepsis patients present particular difficulties as they are at increased risk of a wide range of complications, such as multiple organ failure, neurological dysfunction, septic shock, ARDS, abdominal compartment syndrome, vasoplegic syndrome, and myocardial dysfunction. The development of any one of these complications can cause the patient's rapid deterioration, and each has distinct implications in terms of appropriate and safe forms of sedation. In this way, the present article reviews the sedative and analgesic drugs commonly used in the ICU and, placing special emphasis on their strategic administration in sepsis patients, develops a set of proposals for sedoanalgesia aimed at improving outcomes for this group of patients. These proposals represent a move away from simplistic approaches like avoiding benzodiazepines to more "objective-guided sedation" that accounts for a patient's principal pathology, as well as any comorbidities, and takes full advantage of the therapeutic arsenal currently available to achieve personalised, patient-centred treatment goals.

Precision medicine is a growing field in critical care. Research increasingly demonstrated pharmacogenomic variability to be an important determinant of analgesic and sedative drug response in the intensive care unit (ICU). Genome-wide association and candidate gene finding studies suggest analgesic and sedatives tailored to an individual's genetic makeup, environmental adaptations, in addition to several other patient- and drug-related factors, will maximize effectiveness and help mitigate harm. However, the number of pharmacogenetic studies in ICU patients remains small and no prospective studies have been published using pharmacogenomic data to optimize analgesic or sedative therapy in critically ill patients. Current recommendations for treating ICU pain and agitation are based on controlled studies having low external validity, including the failure to consider pharmacogenomic factors affecting response. Use of a precision medicine approach to individualize pharmacotherapy focused on optimizing ICU patient comfort and safety may improve the outcomes of critically ill adults. Additionally, benefits and risks of analgesic and/or sedative therapy in an individual may be informed with large, standardized datasets. The purpose of this review was to describe a precision medicine approach focused on optimizing analgesic and sedative therapy in individual ICU patients to optimize clinical outcomes and reduce safety concerns.

Brain injured patients often need deep sedation to prevent or treat increased intracranial pressure. The mainly used IV sedatives have side effects and/or high context-sensitive half-lives, limiting their use. Inhalative sedatives have comparatively minor side effects and a brief context-sensitive half-life. Despite the theoretical advantages, evidence in this patient group is lacking. A Germany-wide survey with 21 questions was conducted to find out how widespread the use of inhaled sedation is. An invitation for the survey was sent to 226 leaders of intensive care units (ICU) treating patients with brain injury as listed by the German Society for Neurointensive Care. Eighty-nine participants answered the questionnaire, but not all items were responded to, which resulted in different absolute counts. Most of them (88%) were university or high-level hospital ICU leaders and (67%) were leaders of specialized neuro-ICUs. Of these, 53/81 (65%) use inhalative sedation, and of the remaining 28, 17 reported interest in using this kind of sedation. Isoflurane is used by 43/53 (81%), sevoflurane by 15/53 (28%), and desflurane by 2. Hypotension and mydriasis are the most common reported side effects (25%). The presented survey showed that inhalative sedatives were used in a significant number of intensive care units in Germany to treat severely brain-injured patients.

Sedation is fundamental to the management of patients in the intensive care unit (ICU). Its indications in the ICU are vast, including the facilitating of mechanical ventilation, permitting invasive procedures, and managing anxiety and agitation. Inhaled sedation with halogenated agents, such as isoflurane or sevoflurane, is now feasible in ICU patients using dedicated devices/systems. Its use may reduce adverse events and improve ICU outcomes compared to conventional intravenous (IV) sedation in the ICU. This review examined the effectiveness of inhalational sedation using the anesthetic conserving device (ACD) compared to standard IV sedation for adult patients in ICU and highlights the technical aspects of its functioning.

We searched the PubMed, Cochrane Central Register of Controlled Trials, The Cochrane Library, MEDLINE, Web of Science, and Sage Journals databases using the terms "anesthetic conserving device," "Anaconda," "sedation" and "intensive care unit" in randomized clinical studies that were performed between 2012 and 2022 and compared volatile sedation using an ACD with IV sedation in terms of time to extubation, duration of mechanical ventilation, and lengths of ICU and hospital stay.

Nine trials were included. Volatile sedation (sevoflurane or isoflurane) administered through an ACD shortened the awakening time compared to IV sedation (midazolam or propofol).

Compared to IV sedation, volatile sedation administered through an ACD in the ICU shortened the awakening and extubation times, ICU length of stay, and duration of mechanical ventilation. More clinical trials that assess additional clinical outcomes on a large scale are needed.