ICU- and ventilator-free days with isoflurane or propofol as a primary sedative - A post- hoc analysis of a randomized controlled trial.

PURPOSE: 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. MATERIALS AND METHODS: 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. RESULTS: 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). CONCLUSIONS: Isoflurane via the ACD was not associated with more VFD but with more ICU-FD and less concomitant sedative use.

Ventilatory Effects of Isoflurane Sedation via the Sedaconda ACD-S versus ACD-L: A Substudy of a Randomized Trial.

Devices used to deliver inhaled sedation increase dead space ventilation. We therefore compared ventilatory effects among isoflurane sedation via the Sedaconda ACD-S (internal volume: 50 mL), isoflurane sedation via the Sedaconda ACD-L (100 mL), and propofol sedation with standard mechanical ventilation with heat and moisture exchangers (HME). This is a substudy of a randomized trial that compared inhaled isoflurane sedation via the ACD-S or ACD-L to intravenous propofol sedation in 301 intensive care patients. Data from the first 24 h after study inclusion were analyzed using linear mixed models. Primary outcome was minute ventilation. Secondary outcomes were tidal volume, respiratory rate, arterial carbon dioxide pressure, and isoflurane consumption. In total, 151 patients were randomized to propofol and 150 to isoflurane sedation; 64 patients received isoflurane via the ACD-S and 86 patients via the ACD-L. While use of the ACD-L was associated with higher minute ventilation (average difference (95% confidence interval): 1.3 (0.7, 1.8) L/min, p < 0.001), higher tidal volumes (44 (16, 72) mL, p = 0.002), higher respiratory rates (1.2 (0.1, 2.2) breaths/min, p = 0.025), and higher arterial carbon dioxide pressures (3.4 (1.2, 5.6) mmHg, p = 0.002), use of the ACD-S did not significantly affect ventilation compared to standard mechanical ventilation and sedation. Isoflurane consumption was slightly less with the ACD-L compared to the ACD-S (-0.7 (-1.3, 0.1) mL/h, p = 0.022). The Sedaconda ACD-S compared to the ACD-L is associated with reduced minute ventilation and does not significantly affect ventilation compared to a standard mechanical ventilation and sedation setting. The smaller ACD-S is therefore the device of choice to minimize impact on ventilation, especially in patients with a limited ability to compensate (e.g., COPD patients). Volatile anesthetic consumption is slightly higher with the ACD-S compared to the ACD-L.

Isoflurane vs. propofol for sedation in invasively ventilated patients with acute hypoxemic respiratory failure: an a priori hypothesis substudy of a randomized controlled trial.

BACKGROUND: Acute hypoxemic respiratory failure (AHRF) is a leading concern in critically ill patients. Experimental and clinical data suggest that early sedation with volatile anesthestics may improve arterial oxygenation and reduce the plasma and alveolar levels of markers of alveolar epithelial injury and of proinflammatory cytokines. METHODS: An a priori hypothesis substudy of a multicenter randomized controlled trial (The Sedaconda trial, EUDRA CT Number 2016-004551-67). In the Sedaconda trial, 301 patients on invasive mechanical ventilation were randomized to 48 h of sedation with isoflurane or propofol in a 1:1 ratio. For the present substudy, patients with a ratio of arterial pressure of oxygen (PaO2) to inspired fraction of oxygen (FiO2), PaO2/FiO2, of ≤ 300 mmHg at baseline were included (n = 162). The primary endpoint was the change in PaO2/FiO2 between baseline and the end of study sedation. A subgroup analysis in patients with PaO2/FiO2 ≤ 200 mmHg was performed (n = 82). RESULTS: Between baseline and the end of study sedation (48 h), oxygenation improved to a similar extent in the isoflurane vs. the propofol group (isoflurane: 199 ± 58 to 219 ± 76 mmHg (n = 70), propofol: 202 ± 62 to 236 ± 77 mmHg (n = 89); p = 0.185). On day seven after randomization, PaO2/FiO2 was 210 ± 79 mmHg in the isoflurane group (n = 41) and 185 ± 87 mmHg in the propofol group (n = 44; p = 0.411). In the subgroup of patients with PaO2/FiO2 ≤ 200 mmHg, PaO2/FiO2 increase between baseline and end of study sedation was 152 ± 33 to 186 ± 54 mmHg for isoflurane (n = 37), and 150 ± 38 to 214 ± 85 mmHg for propofol (n = 45; p = 0.029). On day seven, PaO2/FiO2 was 198 ± 69 mmHg in patients randomized to isoflurane (n = 20) and 174 ± 106 mmHg in patients randomized to propofol (n = 20; p = 0.933). Both for the whole study population and for the subgroup with PaO2/FiO2 ≤ 200 mmHg, no significant between-group differences were observed for PaCO2, pH and tidal volume as well as 30-day mortality and ventilator-free days alive. CONCLUSIONS: In patients with AHRF, inhaled sedation with isoflurane for a duration of up to 48 h did not lead to improved oxygenation in comparison to intravenous sedation with propofol. Trial registration The main study was registered in the European Medicines Agency's EU Clinical Trial register (EudraCT), 2016-004551-67, before including the first patient. The present substudy was registered at German Clinical Trials Register (DRKS, ID: DRKS00018959) on January 7th, 2020, before opening the main study data base and obtaining access to study results.

Augmented Reality-Based Surgery on the Human Cadaver Using a New Generation of Optical Head-Mounted Displays: Development and Feasibility Study.

BACKGROUND: Although nearly one-third of the world's disease burden requires surgical care, only a small proportion of digital health applications are directly used in the surgical field. In the coming decades, the application of augmented reality (AR) with a new generation of optical-see-through head-mounted displays (OST-HMDs) like the HoloLens (Microsoft Corp) has the potential to bring digital health into the surgical field. However, for the application to be performed on a living person, proof of performance must first be provided due to regulatory requirements. In this regard, cadaver studies could provide initial evidence. OBJECTIVE: The goal of the research was to develop an open-source system for AR-based surgery on human cadavers using freely available technologies. METHODS: We tested our system using an easy-to-understand scenario in which fractured zygomatic arches of the face had to be repositioned with visual and auditory feedback to the investigators using a HoloLens. Results were verified with postoperative imaging and assessed in a blinded fashion by 2 investigators. The developed system and scenario were qualitatively evaluated by consensus interview and individual questionnaires. RESULTS: The development and implementation of our system was feasible and could be realized in the course of a cadaver study. The AR system was found helpful by the investigators for spatial perception in addition to the combination of visual as well as auditory feedback. The surgical end point could be determined metrically as well as by assessment. CONCLUSIONS: The development and application of an AR-based surgical system using freely available technologies to perform OST-HMD-guided surgical procedures in cadavers is feasible. Cadaver studies are suitable for OST-HMD-guided interventions to measure a surgical end point and provide an initial data foundation for future clinical trials. The availability of free systems for researchers could be helpful for a possible translation process from digital health to AR-based surgery using OST-HMDs in the operating theater via cadaver studies.

Anesthetic gas consumption with target-controlled administration versus a semi-closed circle system with automatic end-tidal concentration control in an artificial lung model.

The use of volatile anesthetics as sedatives in the intensive care unit is relevant to the patient's outcome. We compared anesthetic gas consumption of the conventional semi-closed Aisys CSTM with the MIRUSTM system, which is the first anesthetic gas reflector system that can administer desflurane in addition to isoflurane and sevoflurane. We connected an artificial lung model to either a MIRUSTM system and a Puritan BennettTM 840 ventilator or an Aisys CSTM anesthesia machine. We found that consumption of 0.5% isoflurane, which corresponds to the target concentration 0.5 MAC, was averaged to 2 mL/h in the MIRUSTM system, which is identical to the Aisys CSTM at a fresh gas flow (FGF) of 1.0 L/min. MIRUSTM consumption of 1% sevoflurane was averaged to 10 mL/h, which corresponds to 8.4 mL/h at FGF 2.5 L/min. The MIRUSTM system consumed 3% or 4% desflurane at an average of 13.0 mL/h or 21.3 mL/h, which is between the consumption at 1.0 L/min and 2.5 L/min FGF. Thus, the MIRUSTM system can effectively deliver volatile anesthetics in clinically relevant concentrations in a similar rate as a conventional circular breathing system at FGFs between 1.0 L/min and 2.5 L/min.

In vitro performance evaluation of AnaConDaTM-100 and AnaConDaTM-50 compared to a circle breathing system for control and consumption of volatile anaesthetics.

To identify the better volatile anaesthetic delivery system in an intensive care setting, we compared the circle breathing system and two models of reflection systems (AnaConDa™ with a dead space of 100 ml (ACD-100) or 50 ml (ACD-50)). These systems were analysed for the parameters like wash-in, consumption, and wash-out of isoflurane and sevoflurane utilising a test lung model. The test lung was connected to a respirator (circle breathing system: Aisys CS™; ACD-100/50: Puriton Bennett 840). Set parameters were volume-controlled mode, tidal volume-500 ml, respiratory rate-10/min, inspiration time-2 sec, PEEP-5 mbar, and oxygen-21%. Wash-in, consumption, and wash-out were investigated at fresh gas flows of 0.5, 1.0, 2.5, and 5.0 l/min. Anaesthetic target concentrations were 0.5, 1.0, 1.5, 2.0, and 2.5%.  Wash-in was slower in ACD-100/-50 compared to the circle breathing system, except for fresh gas flows of 0.5 and 1.0 l/min. The consumption of isoflurane and sevoflurane in ACD-100 and ACD-50 corresponded to the fresh gas flow of 0.5-1.0 l/min in the circle breathing system. Consumption with ACD-50 was higher in comparison to ACD-100, especially at gas concentrations > 1.5%. Wash-out was quicker in ACD-100/-50 than in the circle breathing system at a fresh gas flow of 0.5 l/min, however, it was longer at all the other flow rates. Wash-out was comparable in ACD-100 and ACD-50. Wash-in and wash-out were generally quicker with the circle breathing system than in ACD-100/-50. However, consumption at 0.5 minimum alveolar concentration was comparable at flows of 0.5 and 1.0 l/min.

Inhaled Sedation in Patients with COVID-19-Related Acute Respiratory Distress Syndrome: An International Retrospective Study.

BACKGROUND AND OBJECTIVES: The coronavirus disease 2019 (COVID-19) pandemic and the shortage of intravenous sedatives has led to renewed interest in inhaled sedation for patients with acute respiratory distress syndrome (ARDS). We hypothesized that inhaled sedation would be associated with improved clinical outcomes in COVID-19 ARDS patients. METHODS: Retrospective international study including mechanically ventilated patients with COVID-19 ARDS who required sedation and were admitted to 10 European and US intensive care units. The primary endpoint of ventilator-free days through day 28 was analyzed using zero-inflated negative binomial regression, before and after adjustment for site, clinically relevant covariates determined according to the univariate results, and propensity score matching. RESULTS: A total of 196 patients were enrolled, 78 of whom died within 28 days. The number of ventilator-free days through day 28 did not differ significantly between the patients who received inhaled sedation for at least 24 h (n = 111) and those who received intravenous sedation only (n = 85), with medians of 0 (interquartile range [IQR] 0-8) and 0 (IQR 0-17), respectively (odds ratio for having zero ventilator-free days through day 28, 1.63, 95% confidence interval [CI], 0.91-2.92, p = 0.10). The incidence rate ratio for the number of ventilator-free days through day 28 if not 0 was 1.13 (95% CI, 0.84-1.52, p = 0.40). Similar results were found after multivariable adjustment and propensity matching. CONCLUSION: The use of inhaled sedation in COVID-19 ARDS was not associated with the number of ventilator-free days through day 28.

Extracorporeal membrane oxygenation and inhaled sedation in coronavirus disease 2019-related acute respiratory distress syndrome.

Coronavirus disease 2019 (COVID-19) related acute respiratory distress syndrome (ARDS) is a severe complication of infection with severe acute respiratory syndrome coronavirus 2, and the primary cause of death in the current pandemic. Critically ill patients often undergo extracorporeal membrane oxygenation (ECMO) therapy as the last resort over an extended period. ECMO therapy requires sedation of the patient, which is usually achieved by intravenous administration of sedatives. The shortage of intravenous sedative drugs due to the ongoing pandemic, and attempts to improve treatment outcome for COVID-19 patients, drove the application of inhaled sedation as a promising alternative for sedation during ECMO therapy. Administration of volatile anesthetics requires an appropriate delivery. Commercially available ones are the anesthetic gas reflection systems AnaConDa® and MIRUSTM, and each should be combined with a gas scavenging system. In this review, we describe respiratory management in COVID-19 patients and the procedures for inhaled sedation during ECMO therapy of COVID-19 related ARDS. We focus particularly on the technical details of administration of volatile anesthetics. Furthermore, we describe the advantages of inhaled sedation and volatile anesthetics, and we discuss the limitations as well as the requirements for safe application in the clinical setting.

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.

BACKGROUND: Previous studies indicate that isoflurane could be useful for the sedation of patients in the intensive care unit (ICU), but prospective studies evaluating isoflurane's efficacy have been small. The aim of this study was to test whether the sedation with isoflurane was non-inferior to sedation with propofol. METHODS: This phase 3, randomised, controlled, open-label non-inferiority trial evaluated the efficacy and safety of up to 54 h of isoflurane compared with propofol in adults (aged ≥18 years) who were invasively ventilated in ICUs in Germany (21 sites) and Slovenia (three sites). Patients were randomly assigned (1:1) to isoflurane inhalation via the Sedaconda anaesthetic conserving device (ACD; Sedana Medical AB, Danderyd, Sweden; ACD-L [dead space 100 mL] or ACD-S [dead space 50 mL]) or intravenous propofol infusion (20 mg/mL) for 48 h (range 42-54) using permuted block randomisation with a centralised electronic randomisation system. The primary endpoint was percentage of time in Richmond Agitation-Sedation Scale (RASS) range -1 to -4, assessed in eligible participants with at least 12 h sedation (the per-protocol population), five or more RASS measurements, and no major protocol violations, with a non-inferiority margin of 15%. Key secondary endpoints were opioid requirements, spontaneous breathing, time to wake-up and extubation, and adverse events. Safety was assessed in all patients who received at least one dose. The trial is complete and registered with EudraCT, 2016-004551-67. FINDINGS: Between July 2, 2017, and Jan 12, 2020, 338 patients were enrolled and 301 (89%) were randomly assigned to isoflurane (n=150) or propofol (n=151). 146 patients (97%) in each group completed the 24-h follow-up. 146 (97%) patients in the isoflurane group and 148 (98%) of patients in the propofol group were included in the per-protocol analysis of the primary endpoint. Least-squares mean percentage of time in RASS target range was 90·7% (95% CI 86·8-94·6) for isoflurane and 91·1% (87·2-95·1) for propofol. With isoflurane sedation, opioid dose intensity was 29% lower than with propofol for the overall sedation period (0·22 [0·12-0·34] vs 0·32 [0·21-0·42] mg/kg per h morphine equivalent dose, p=0·0036) and spontaneous breathing was more frequent on day 1 (odds ratio [OR] 1·72 [1·12-2·64], generalised mixed linear model p=0·013, with estimated rates of 50% of observations with isoflurane vs 37% with propofol). Extubation times were short and median wake-up was significantly faster after isoflurane on day 2 (20 min [IQR 10-30] vs 30 min [11-120]; Cox regression p=0·0011). The most common adverse events by treatment group (isoflurane vs propofol) were: hypertension (ten [7%] of 150 vs two [1%] of 151), delirium (eight [5%] vs seven [5%]), oliguria (seven [5%] vs six [4%]), and atrial fibrillation (five [3%] vs four [3%]). INTERPRETATION: These results support the use of isoflurane in invasively ventilated patients who have a clinical need for sedation. FUNDING: Sedana Medical AB.

Spontaneous breathing for managing analgesia during balanced anesthesia with remifentanil and desflurane: a prospective, single center randomized controlled trial.

The main goal of anesthesiology is to achieve the best level of analgesia and a fast recovery of consciousness following anesthesia. The preservation of spontaneous breathing during general anesthesia with anesthetic gases is practiced by many anesthetists. However, very few studies have dealt with these positive properties of volatile anesthetics such as sevoflurane or desflurane. Remifentanil is a very short half-life opiate that combines sufficient intra-operative analgesia with a fast post-operative recovery time. We tested the hypothesis that spontaneous breathing can reduce overdosing with remifentanil during desflurane anesthesia. In this prospective, single center, multiple anesthetist study, 30 patients were randomized into two groups (volume-controlled ventilation mode and spontaneous breathing). The spontaneous breathing group showed a significantly lower post-operative pain level than the volume-controlled ventilation mode group. Furthermore, less remifentanil as well as less piritramide was needed in the spontaneous breathing group compared with volume-controlled ventilation mode. It was possible to achieve spontaneous breathing in all patients with 0.6 minimum alveolar concentration desflurane, in order to control the remifentanil rate and prevent an overdose. All spontaneous breathing patients had low intra- and post-operative pain levels and the need for analgesics was equal to or lower than that in the volume-controlled ventilation mode group. By reducing the intra-operative amount of opiates, both the post-operative pain and the amount of post-operative analgesia required can be reduced. A balanced anesthesia with spontaneous intra-operative breathing is needed to determine the required amount of opiates. This study was approved by the Ethic Committee of the Ruhr-University of Bochum (approval No. 2435) in September, 2004.

Negative drift of sedation depth in critically ill patients receiving constant minimum alveolar concentration of isoflurane, sevoflurane, or desflurane: a randomized controlled trial.

BACKGROUND: Intensive care unit (ICU) physicians have extended the minimum alveolar concentration (MAC) to deliver and monitor long-term volatile sedation in critically ill patients. There is limited evidence of MAC's reliability in controlling sedation depth in this setting. We hypothesized that sedation depth, measured by the electroencephalography (EEG)-derived Narcotrend-Index (burst-suppression N_Index 0-awake N_Index 100), might drift downward over time despite constant MAC values. METHODS: This prospective single-centre randomized clinical study was conducted at a University Hospital Surgical Intensive Care Unit and included consecutive, postoperative ICU patients fulfilling the inclusion criteria. Patients were randomly assigned to receive uninterrupted inhalational sedation with isoflurane, sevoflurane, or desflurane. The end-expiratory concentration of the anaesthetics and the EEG-derived index were measured continuously in time-stamped pairs. Sedation depth was also monitored using Richmond-Agitation-Sedation-Scale (RASS). The paired t-test and linear models (bootstrapped or multilevel) have been employed to analyze MAC, N_Index and RASS across the three groups. RESULTS: Thirty patients were recruited (female/male: 10/20, age 64 ± 11, Simplified Acute Physiology Score II 30 ± 10). In the first 24 h, 21.208 pairs of data points (N_Index and MAC) were recorded. The median MAC of 0.58 ± 0.06 remained stable over the sedation time in all three groups. The t-test indicated in the isoflurane and sevoflurane groups a significant drop in RASS and EEG-derived N_Index in the first versus last two sedation hours. We applied a multilevel linear model on the entire longitudinal data, nested per patient, which produced the formula N_Index = 43 - 0.7·h (R2 = 0.76), showing a strong negative correlation between sedation's duration and the N_Index. Bootstrapped linear models applied for each sedation group produced: N_Index of 43-0.9, 45-0.8, and 43-0.4·h for isoflurane, sevoflurane, and desflurane, respectively. The regression coefficient for desflurane was almost half of those for isoflurane and sevoflurane, indicating a less pronounced time-effect in this group. CONCLUSIONS: Maintaining constant MAC does not guarantee stable sedation depth. Thus, the patients necessitate frequent clinical assessments or, when unfeasible, continuous EEG monitoring. The differences across different volatile anaesthetics regarding their time-dependent negative drift requires further exploration. TRIAL REGISTRATION: NCT03860129.

Washout and Awakening Times after Inhaled Sedation of Critically Ill Patients: Desflurane Versus Isoflurane.

In recent years, inhaled sedation has been increasingly used in the intensive care unit (ICU). The aim of this prospective, controlled trial was to compare washout and awakening times after long term sedation with desflurane and isoflurane both administered with the Mirus™ system (TIM GmbH, Koblenz, Germany). Twenty-one consecutive critically ill patients were alternately allocated to the two study groups, obtaining inhaled sedation with either desflurane or isoflurane. After 24 h study sedation, anesthetic washout curves were recorded, and a standardized wake-up test was performed. The primary outcome measure was the time required to decrease the endtidal concentration to 50% (T50%). Secondary outcome measures were T80% and awakening times (all extremities moved, RASS -2). Decrement times (min) (desflurane versus isoflurane, median (1st quartile-3rd quartile)) (T50%: 0.3 (0.3-0.4) vs. 1.3 (0.4-2.3), log-rank test P = 0.002; P80%: 2.5 (2-5.9) vs. 12.1 (5.1-20.2), P = 0.022) and awakening times (to RASS -2: 7.5 (5.5-8.8) vs. 41.0 (24.5-43.0), P = 0.007; all extremities moved: 5.0 (4.0-8.5) vs. 13.0 (8.0-41.25), P = 0.037) were significantly shorter after desflurane compared to isoflurane. The use of desflurane with the Mirus™ system significantly shortens the washout times and leads to faster awakening after sedation of critically ill patients.

High dose ibuprofen as a monotherapy on an around-the-clock basis fails to control pain in children undergoing tonsil surgery: a prospective observational cohort study.

PURPOSE: The optimal pain management concept in children after tonsil surgery is controversial. Ibuprofen on an "around-the-clock" basis has been suggested to control postoperative pain sufficiently. Therefore, we established a standard scheme with weight-adapted recommended maximum ibuprofen dose. A reliable assessment of pain intensity can be performed with the Children's and Infants' Postoperative Pain Scale (CHIPPS) in children < 5 years, or with the Faces Pain Scale-Revised (FPS-R) in children aged ≥ 5 years. The Parents' Postoperative Pain Measure (PPPM-D) may be a useful tool for both age groups. We hypothesized that not more than 30% of the children would need an opioid rescue medication during their in-hospital stay and analyzed the consistency of the PPPM-D with other pain scales. METHODS: We included 158 in-patients aged 2-12 years. Ibuprofen was orally administered every 8 h. Three times daily, pain scores were assessed by CHIPPS or FPS-R, respectively. The PPPM-D was used in all children. Exceeding the cut-off value in one of the tools was regarded as relevant pain. RESULTS: A rescue medication was needed in 82.1% of children after tonsillectomy and 51.3% of children after tonsillotomy (P < 0.001). The cut-off value for relevant pain was mostly exceeded in the PPPM-D, but its overall concordance to the reference scales was low. CONCLUSION: High-dose ibuprofen "around-the-clock" is insufficient to control pain in children after tonsil surgery. Research is needed to find an optimal schema for management and assessment of postoperative pain.

Comparison of 3 Methods to Assess Occupational Sevoflurane Exposure in Abdominal Surgeons: A Single-Center Observational Pilot Study.

BACKGROUND: Studies demonstrated that operating room personnel are exposed to anesthetic gases such as sevoflurane (SEVO). Measuring the gas burden is essential to assess the exposure objectively. Air pollution measurements and the biological monitoring of urinary SEVO and its metabolite hexafluoroisopropanol (HFIP) are possible approaches. Calculating the mass of inhaled SEVO is an alternative, but its predictive power has not been evaluated. We investigated the SEVO burdens of abdominal surgeons and hypothesized that inhaled mass calculations would be better suited than pollution measurements in their breathing zones (25 cm around nose and mouth) to estimate urinary SEVO and HFIP concentrations. The effects of potentially influencing factors were considered. METHODS: SEVO pollution was continuously measured by photoacoustic gas monitoring. Urinary SEVO and HFIP samples, which were collected before and after surgery, were analyzed by a blinded environmental toxicologist using the headspace gas chromatography-mass spectrometry method. The mass of inhaled SEVO was calculated according to the formula mVA = cVA·(Equation is included in full-text article.)·t·ρ VA aer. (mVA: inhaled mass; cVA: volume concentration; (Equation is included in full-text article.): respiratory minute volume; t: exposure time; and ρ VA aer.: gaseous density of SEVO). A linear multilevel mixed model was used for data analysis and comparisons of the different approaches. RESULTS: Eight surgeons performed 22 pancreatic resections. Mean (standard deviation [SD]) SEVO pollution was 0.32 ppm (0.09 ppm). Urinary SEVO concentrations were below the detection limit in all samples, whereas HFIP was detectable in 82% of the preoperative samples in a mean (SD) concentration of 8.53 µg·L (15.53 µg·L; median: 2.11 µg·L, interquartile range [IQR]: 4.58 µg·L) and in all postoperative samples (25.42 µg·L [21.39 µg·L]). The mean (SD) inhaled SEVO mass was 5.67 mg (2.55 mg). The postoperative HFIP concentrations correlated linearly to the SEVO concentrations in the surgeons' breathing zones (ß = 216.89; P < .001) and to the calculated masses of inhaled SEVO (ß = 4.17; P = .018). The surgeon's body mass index (BMI), age, and the frequency of surgeries within the last 24 hours before study entry did not influence the relation between HFIP concentration and air pollution or inhaled mass, respectively. CONCLUSIONS: The biological SEVO burden, expressed as urinary HFIP concentration, can be estimated by monitoring SEVO pollution in the personnel's individual breathing zone. Urinary SEVO was not an appropriate biomarker in this setting.

Use of MIRUS™ for MAC-driven application of isoflurane, sevoflurane, and desflurane in postoperative ICU patients: a randomized controlled trial.

BACKGROUND: The MIRUS™ (TIM, Koblenz, Germany) is an electronical gas delivery system, which offers an automated MAC (minimal alveolar concentration)-driven application of isoflurane, sevoflurane, or desflurane, and can be used for sedation in the intensive care unit. We investigated its consumption of volatile anesthetics at 0.5 MAC (primary endpoint) and the corresponding costs. Secondary endpoints were the technical feasibility to reach and control the MAC automatically, the depth of sedation at 0.5 MAC, and awakening times. Mechanically ventilated and sedated patients after major surgery were enrolled. Upon arrival in the intensive care unit, patients obtained intravenous propofol sedation for at least 1 h to collect ventilation and blood gas parameters, before they were switched to inhalational sedation using MIRUS™ with isoflurane, sevoflurane, or desflurane. After a minimum of 2 h, inhalational sedation was stopped, and awakening times were recorded. A multivariate electroencephalogram and the Richmond Agitation Sedation Scale (RASS) were used to assess the depth of sedation. Vital signs, ventilation parameters, gas consumption, MAC, and expiratory gas concentrations were continuously recorded. RESULTS: Thirty patients obtained inhalational sedation for 18:08 [14:46-21:34] [median 1st-3rd quartiles] hours. The MAC was 0.58 [0.50-0.64], resulting in a Narcotrend Index of 37.1 [30.9-42.4] and a RASS of - 3.0 [- 4.0 to (- 3.0)]. The median gas consumption was significantly lowest for isoflurane ([ml h-1]: isoflurane: 3.97 [3.61-5.70]; sevoflurane: 8.91 [6.32-13.76]; and desflurane: 25.88 [20.38-30.82]; p < 0.001). This corresponds to average costs of 0.39 € h-1 for isoflurane, 2.14 € h-1 for sevoflurane, and 7.54 € h-1 for desflurane. Awakening times (eye opening [min]: isoflurane: 9:48 [4:15-20:18]; sevoflurane: 3:45 [0:30-6:30]; desflurane: 2:00 [1:00-6:30]; p = 0.043) and time to extubation ([min]: isoflurane: 10:10 [8:00-20:30]; sevoflurane: 7:30 [4:37-14:22]; desflurane: 3:00 [3:00-6:00]; p = 0.007) were significantly shortest for desflurane. CONCLUSIONS: A target-controlled, MAC-driven automated application of volatile anesthetics is technically feasible and enables an adequate depth of sedation. Gas consumption was highest for desflurane, which is also the most expensive volatile anesthetic. Although awakening times were shortest, the actual time saving of a few minutes might be negligible for most patients in the intensive care unit. Thus, using desflurane seems not rational from an economic perspective. Trial registration Clinical Trials Registry (ref.: NCT03860129). Registered 24 September 2018-Retrospectively registered.

Photoacoustic gas monitoring for anesthetic gas pollution measurements and its cross-sensitivity to alcoholic disinfectants.

BACKGROUND: Real-time photoacoustic gas monitoring is used for personnel exposure and environmental monitoring, but its accuracy varies when organic solvents such as alcohol contaminate measurements. This is problematic for anesthetic gas measurements in hospitals, because most disinfectants contain alcohol, which could lead to false-high gas concentrations. We investigated the cross-sensitivities of the photoacoustic gas monitor Innova 1412 (AirTech Instruments, LumaSense, Denmark) against alcohols and alcoholic disinfectants while measuring sevoflurane, desflurane and isoflurane in a laboratory and in hospital during surgery. METHODS: 25 mL ethyl alcohol was distributed on a hotplate. An optical filter for isoflurane was used and the gas monitor measured the 'isoflurane' concentration for five minutes with the measuring probe fixed 30 cm above the hotplate. Then, 5 mL isoflurane was added vaporized via an Anesthetic Conserving Device (Sedana Medical, Uppsala, Sweden). After one-hour measurement, 25 mL isopropyl alcohol, N-propanol, and two alcoholic disinfectants were subsequently added, each in combination with 5 mL isoflurane. The same experiment was in turn performed for sevoflurane and desflurane. The practical impact of the cross-sensitivity was investigated on abdominal surgeons who were exposed intraoperatively to sevoflurane. A new approach to overcome the gas monitor's cross-sensitivity is presented. RESULTS: Cross-sensitivity was observed for all alcohols and its strength characteristic for the tested agent. Simultaneous uses of anesthetic gases and alcohols increased the concentrations and the recovery times significantly, especially while sevoflurane was utilized. Intraoperative measurements revealed mean and maximum sevoflurane concentrations of 0.61 ± 0.26 ppm and 15.27 ± 14.62 ppm. We replaced the cross-sensitivity peaks with the 10th percentile baseline of the anesthetic gas concentration. This reduced mean and maximum concentrations significantly by 37% (p < 0.001) and 86% (p < 0.001), respectively. CONCLUSION: Photoacoustic gas monitoring is useful to detect lowest anesthetic gases concentrations, but cross-sensitivity caused one third falsely high measured mean gas concentration. One possibility to eliminate these peaks is the recovery time-based baseline approach. Caution should be taken while measuring sevoflurane, since marked cross-sensitivity peaks are to be expected.

Kinetics of isoflurane and sevoflurane in a unidirectional displacement flow and the relevance to anesthetic gas exposure by operating room personnel.

International guidelines recommend the use of ventilation systems in operating rooms to reduce the concentration of potentially hazardous substances such as anesthetic gases. The exhaust air grilles of these systems are typically located in the lower corners of the operating room and pick up two-thirds of the air volume, whereas the final third is taken from near the ceiling, which guarantees an optimal perfusion of the operating room with a sterile filtered air supply. However, this setup is also employed because anesthetic gases have a higher molecular weight than the components of air and should pool on the floor if movement is kept to a minimum and if a ventilation system with a unidirectional displacement flow is employed. However, this anticipated pooling of volatile anesthetics at the floor level has never been proven. Thus, we herein investigated the flow behaviors of isoflurane, sevoflurane, and carbon dioxide (for comparison) in a measuring chamber sized 2.46 × 1.85 × 5.40 m with a velocity of 0.3 m/sec and a degree of turbulence <20%. Gas concentrations were measured at 1,728 measuring positions throughout the measuring chamber, and the flow behaviors of isoflurane and sevoflurane were found to be similar, with an overlap of 90%. The largest spread of both gases was 55 cm at 5.4 m from the emission source. Interestingly, neither isoflurane nor sevoflurane was detected at floor level, but a continuous cone-like spreading was observed due to gravity. In contrast, carbon dioxide accumulated at floor level in the form of a gas cloud. Thus, floor level exhaust ventilation systems are likely unsuitable for the collection and removal of anesthetic gases from operating rooms.

The Personnel's Sevoflurane Exposure in the Postanesthesia Care Unit Measured by Photoacoustic Gas Monitoring and Hexafluoroisopropanol Biomonitoring.

PURPOSE: Room ventilation in the postanesthesia care unit (PACU) is often poor, although patients exhale anesthetic gases. We investigated the PACU personnel's environmental and biological sevoflurane (SEVO) burden during patient care. DESIGN: Prospective, observational study. METHODS: Air pollution was measured by photoacoustic gas monitoring in the middle of the PACU, above the patient's face, and on the PACU corridor. Urinary SEVO and hexafluoroisopropanol concentrations were determined. FINDINGS: Mean air pollution was 0.34 ± 0.07 ppm in the middle of the PACU, 0.56 ± 0.17 ppm above the patient's face, and 0.47 ± 0.06 ppm on the corridor. Biological preshift exposure levels were 0.13 ± 0.03 mcg/L (SEVO) and 4.72 ± 5.41 mcg/L (hexafluoroisopropanol). Postshift concentrations increased significantly to 0.20 ± 0.06 mcg/L (P = .004) and 42.18 ± 27.82 mcg/L (P < .001). CONCLUSIONS: PACU personnel were environmentally and biologically exposed to SEVO, but exposure levels were minimal according to current recommendations.

Environmental safety: Air pollution while using MIRUS™ for short-term sedation in the ICU.

BACKGROUND: MIRUS™ is a device for target-controlled inhalational sedation in the ICU in combination with use of isoflurane, or sevoflurane, or desflurane. The feasibility of this device has recently been proven; however, ICU staff exposure may restrict its application. We investigated ICU ambient room pollution during daily work to estimate ICU personnel exposure while using MIRUS™. METHODS: This observational study assessed pollution levels around 15 adult surgical patients who received volatile anaesthetics-based sedation for a median of 11 hours. Measurements were performed by photoacoustic gas monitoring in real-time at different positions near the patient and in the personnel's breathing zone. Additionally, the impact of the Clean Air™ open reservoir scavenging system on volatile agent pollution was evaluated. RESULTS: Baseline concentrations [ppm] during intervention and rest periods were isoflurane c¯mean = 0.58 ± 0.49, c¯max = 5.72; sevoflurane c¯mean = 0.22 ± 0.20, c¯max = 7.93; and desflurane c¯mean = 0.65 ± 0.57, c¯max = 6.65. Refilling MIRUS™ with liquid anaesthetic yielded gas concentrations of c¯mean = 2.18 ± 1.48 ppm and c¯max = 13.03 ± 9.37 ppm in the personnel's breathing zone. Air pollution in the patient's room was approximately five times higher without a scavenging system. CONCLUSION: Ambient room pollution was minimal in most cases, and the measured values were within or below the recommended exposure limits. Caution should be taken during refilling of the MIRUS™ system, as this was accompanied by higher pollution levels. The combined use of air-conditioning and gas scavenging systems is strongly recommended.