H4K20me3 marks distal intergenic and repetitive regions in human mature spermatozoa.

Sperm histones represent an essential part of the paternally transmitted epigenome, but uncertainty exists about the role of those remaining in non-coding and repetitive DNA. We therefore analyzed the genome-wide distribution of the heterochromatic marker H4K20me3 in human sperm and somatic (K562) cells. To specify the function of sperm histones, we compared all H4K20me3-containing and -free loci in the sperm genome. Sperm and somatic cells possessed a very similar H4K20me3 distribution: H4K20me3 peaks occurred mostly in distal intergenic regions and repetitive gene clusters (in particular genes encoding odorant-binding factors and zinc-finger antiviral proteins). In both cell types, H4K20me3 peaks were enriched in LINEs, ERVs, satellite DNA and low complexity repeats. In contrast, H4K20me3-free nucleosomes occurred more frequently in genic regions (in particular promoters, exons, 5'-UTR and 3'-UTR) and were enriched in genes encoding developmental factors (in particular transcription activators and repressors). H4K20me3-free nucleosomes were also detected in substantial quantities in distal intergenic regions and were enriched in SINEs. Thus, evidence suggests that paternally transmitted histones may have a dual purpose: maintenance and regulation of heterochromatin and guidance towards transcription of euchromatin.

In Vitro Model of Prepacked Carbon Dioxide Absorber Use: Development and Testing.

BACKGROUND: Carbon dioxide absorbers allow the use of fresh gas flow below minute ventilation (V˙E). Models are developed and tested in vitro to quantify their performance with variable carbon dioxide load (V˙CO2), fresh gas flow, V˙E, end-tidal carbon dioxide (ETco2) fraction, and the type of workstation used. METHODS: First principles are used to derive a linear relationship between fresh gas flow and fractional canister usage or FCU0.5 (the reciprocal of the time for the inspiratory carbon dioxide fraction to reach 0.5%). This forms the basis for two basic models in which V˙E was measured by spirometry or calculated. These models were extended by multiplying V˙E with an empirical workstation factor. To validate the four models, two hypotheses were tested. To test whether the FCU0.5 intercept varied proportionally with V˙CO2 and was independent of V˙E, FCU was measured for 10 canisters tested with a fixed 0.3 l/min fresh gas flow and a range of V˙CO2 while V˙E was either constant or adjusted to maintain ETco2 fraction. A t test was used to compare the two groups. To confirm whether a change in V˙CO2 accompanied by a change in V˙E to maintain ETco2 fraction would shift the linear fresh gas flow-FCU0.5 relationship in a parallel manner, 19 canisters were tested with different combinations of V˙CO2 and fresh gas flow. These measured FCU values were compared to those predicted by the four models using Varvel's performance criteria. RESULTS: With 0.3 l/min fresh gas flow, FCU0.5 was proportional with V˙CO2 and independent of whether V˙E was adjusted to maintain ETco2 fraction or not (P = 0.962). The hypothesized parallel shift of the fresh gas flow-FCU0.5 relationship was confirmed. Both extended models are good candidate models. CONCLUSIONS: The models predict prepacked canister performance in vitro over the range of V˙E, fresh gas flow, and V˙CO2 likely to be encountered in routine clinical practice. In vivo validation is still needed.

Swallowing outcomes after transoral robotic surgery and adjuvant treatment in unknown primary.

OBJECTIVES: Robotic transoral mucosectomy of the base of tongue was introduced as a diagnostic procedure in patients treated for head and neck cancer with unknown primary (CUP), increasing the identification rate of the primary tumour. For the treatment of CUP, a considerable percentage of patients require adjuvant (chemo)radiation. The aim of this study was to investigate swallowing outcomes among CUP patients after TORS and adjuvant treatment. SUBJECTS AND METHODS: A systematic review was carried out on studies investigating the impact of TORS and adjuvant treatment on swallowing-related outcomes among CUP patients In addition, a cross-sectional study was carried out on swallowing problems (measured using the SWAL-QOL questionnaire) among CUP patients in routine care who visited the outpatient clinic 1-5 years after TORS and adjuvant treatment. RESULTS: The systematic review (6 studies; n = 98) showed that most patients returned to a full oral diet. The cross-sectional study (n = 12) showed that all patients were able to return to a full oral diet, nevertheless, 50% reported swallowing problems in daily life (SWAL-QOL total score ≥14). CONCLUSION: Although after TORS and adjuvant treatment for CUP a full oral diet can be resumed, patients still experience problems with eating and drinking in daily life.

Surgery versus sclerotherapy versus combined therapy in head and neck lymphatic malformations in the pediatric population: systematic review and meta-analysis.

PURPOSE: To systematically review current literature on the treatment of lymphatic malformations (LMs) of the head and neck to guide treatment strategy. METHODS AND MATERIALS: A systematic review and meta-analysis of literature until 16 November 2021 was performed on treatments of LMs in the head and neck. RESULTS: Out of 9044 articles, 54 studies were eligible for inclusion with 26 studies providing detailed participant data. A total number of 1573 patients with a mean age of 21.22 months were analysed. Comparative meta-analysis did not reveal significant differences two proportions of volume reduction (≥ 50% and 100%) between sclerotherapy and surgical treatment. Regression demonstrated that positive predictors for volume reduction were surgery 17 (95% CI 0.26-34; p = 0.047) and treatment of macrocystic lesions 19 (95% CI 5.5-32; p = 0.006). Treatment of mixed lesions also demonstrated a trend towards achieving a greater volume reduction (p = 0.052). A higher de Serres stage of the lesion had a negative effect on the amount of volume reduction - 3.7 (95% CI - 7.0 to - 0.35; p = 0.030). CONCLUSION: This comprehensive meta-analysis demonstrated no significant difference in volume reduction between various treatment modalities at study level. However, individual patient data indicated that surgery and larger cyst types are associated with a significant higher percentage of volume reduction, whereas a higher de Serres stage negatively impacted the amount of volume reduction. These findings can be used for patient counseling and treatment planning based on cyst type and de Serres stage. However volume reduction constitutes just one objective within a more complex treatment spectrum.

Development and validation of a model to calculate anesthetic agent consumption from inspired and end-expired concentrations, minute ventilation, fresh gas flow and dead space ventilation.

Anesthetic agent consumption is often calculated as the product of fresh gas flow (FGF) and vaporizer dial setting (FVAP). Because FVAP of conventional vaporizers is not registered in automated anesthesia records, retrospective agent consumption studies are hampered. The current study examines how FVAP can be retrospectively calculated from the agent's inspired (FIN) and end-expired concentration (FET), FGF, and minute ventilation (MV). Theoretical analysis of agent mass balances in the circle breathing reveals FVAP = [FIN - (dead space fraction * FIN + (1 - dead space fraction) * FET) * (1 - FGF/MV)]/(1-(1 - FGF/MV)). FIN, FET, FGF and MV are routinely monitored, but dead space fraction is unknown. Dead space fraction for sevoflurane, desflurane, and isoflurane was therefore determined empirically from an unpublished data set of 161 patient containing FVAP, FIN, FET, MV and FGF ranging from 0.25 to 8 L/min delivered via an ADU® (GE, Madison, WI, USA). Dead space fraction for each agent was determined empirically by having Excel's solver function calculate the value of dead space fraction that minimized the sum of the squared differences between dialed FVAP and predicted FVAP. With dead space fraction known, the model was then prospectively tested for sevoflurane in O2/air using data collected over the course of two weeks with one FLOW-i (Getinge, Solna, Sweden) and one Zeus workstation (Dräger, Lübeck, Germany). Because both workstations use an electronically controlled vaporizer/injector, the dialed FVAP were available to allow the calculation of median performance error (MDPE) and median absolute performance error (MDAPE). MDPE and MDAP are reported as median and interquartiles. The empirical dead space fraction for isoflurane, sevoflurane, and desflurane were 0.59, 0.49, and 0.66, respectively. For prospective testing, a total of 149.4 h of useful data were collected from 78 patient with the Zeus and Flow-i combined, with FGF ranging from 0.18 to 8 L/min. The model predicted dialed FVAP well, with a MDPE of -1 (-11, 6) % and MDAPE of 8 (4, 17) %. FVAP can be retrospectively calculated from FIN, FET, FGF, and MV plus an agent specific dead space fraction factor with a degree of error that we believe suffices for retrospective sevoflurane consumption analyses. Performance with other agents and N2O awaits further validation.

Arterial to end-tidal CO2 gradients during isocapnic hyperventilation.

Isocapnic hyperventilation (ICHV) is occasionally used to maintain the end-expired CO2 partial pressure (PETCO2) when the inspired CO2 (PICO2) rises. Whether maintaining PETCO2 with ICHV during an increase of the PICO2 also maintains arterial PCO2 (PaCO2) remains poorly documented. 12 ASA PS I-II subjects undergoing a robot-assisted radical prostatectomy (RARP) (n = 11) or cystectomy (n = 1) under general endotracheal anesthesia with sevoflurane in O2/air (40% inspired O2) were enrolled. PICO2 was sequentially increased from 0 to 0.5, 1.0, 1.5 and 2% by adding CO2 to the inspiratory limb of the circle system, while increasing ventilation to a target PETCO2 of 4.7-4.9% by adjusting respiratory rate during controlled mechanical ventilation. Pa-ETCO2 gradients were determined after a 15 min equilibration period at each PICO2 level and compared using ANOVA. Mean (standard deviation) age, height, and weight were 66 (6) years, 171 (6) cm, and 75 (8) kg, respectively. Capnograms were normal and hemodynamic parameters remained stable. PETCO2 could be maintained within 4.7-4.9% in all subjects at all times except in 1 subject with 1.5% PICO2 and 5 subjects with 2.0% PICO2; data from the one subject in whom both 1.5 and 2.0% PICO2 resulted in PETCO2 > 5.1% were excluded from analysis. Pa-ETCO2 gradients did not change when PICO2 increased. The effect of a modest rise of PICO2 up to 1.5% on PETCO2 during RARP can be readily overcome by increasing ventilation without altering the Pa-ETCO2 gradients. At higher PICO2, airway pressures may become a limiting factor, which requires further study.

Practice of oxygen use in anesthesiology - a survey of the European Society of Anaesthesiology and Intensive Care.

BACKGROUND: Oxygen is one of the most commonly used drugs by anesthesiologists. The World Health Organization (WHO) gave recommendations regarding perioperative oxygen administration, but the practice of oxygen use in anesthesia, critical emergency, and intensive care medicine remains unclear. METHODS: We conducted an online survey among members of the European Society of Anaesthesiology and Intensive Care (ESAIC). The questionnaire consisted of 46 queries appraising the perioperative period, emergency medicine and in the intensive care, knowledge about current recommendations by the WHO, oxygen toxicity, and devices for supplemental oxygen therapy. RESULTS: Seven hundred ninety-eight ESAIC members (2.1% of all ESAIC members) completed the survey. Most respondents were board-certified and worked in hospitals with > 500 beds. The majority affirmed that they do not use specific protocols for oxygen administration. WHO recommendations are unknown to 42% of respondents, known but not followed by 14%, and known and followed by 24% of them. Respondents prefer inspiratory oxygen fraction (FiO2) ≥80% during induction and emergence from anesthesia, but intraoperatively < 60% for maintenance, and higher FiO2 in patients with diseased than non-diseased lungs. Postoperative oxygen therapy is prescribed more commonly according to peripheral oxygen saturation (SpO2), but shortage of devices still limits monitoring. When monitoring is used, SpO2 ≤ 95% is often targeted. In critical emergency medicine, oxygen is used frequently in patients aged ≥80 years, or presenting with respiratory distress, chronic obstructive pulmonary disease, myocardial infarction, and stroke. In the intensive care unit, oxygen is mostly targeted at 96%, especially in patients with pulmonary diseases. CONCLUSIONS: The current practice of perioperative oxygen therapy among respondents does not follow WHO recommendations or current evidence, and access to postoperative monitoring devices impairs the individualization of oxygen therapy. Further research and additional teaching about use of oxygen are necessary.

The science behind banning desflurane: A narrative review.

Potent inhaled anaesthetics are halogenated hydrocarbons with a large global warming effect. The use of fluorinated hydrocarbons (most are not anaesthetics) are being restricted but volatile anaesthetics have been exempted from legislation, until now: the EU has formulated a proposal to ban or at least severely restrict the use of desflurane starting January 2026. This narrative review addresses the implications of a politics-driven decision - without prior consultation with major stakeholders, such as the European Society of Anaesthesiology and Intensive Care (ESAIC) - on daily anaesthesia practice and reviews the potential scientific arguments that would support stopping the routine use of desflurane in anaesthetic practice. Of note, banning or severely restricting the use of one anaesthetic agent should not distract the user from sensible interventions like reducing fresh gas flows and developing technology to capture and recycle or destroy the wasted potent inhaled anaesthetics that we will continue to use. We call to join efforts to minimise our professional environmental footprint.

Prospective validation of gas man simulations of sevoflurane in O2/air over a wide fresh gas flow range.

The use of inhaled anesthetics has come under increased scrutiny because of their environmental effects. This has led to a shift where sevoflurane in O2/air has become the predominant gas mixture to maintain anesthesia. To further reduce environmental impact, lower fresh gas flows (FGF) should be used. An accurate model of sevoflurane consumption allows us to assess and quantify the impact of the effects of lowering FGFs. This study therefore tested the accuracy of the Gas Man® model by determining its ability to predict end-expired sevoflurane concentrations (FETsevo) in patients using a protocol spanning a wide range of FGF and vaporizer settings. After IRB approval, 28 ASA I-II patients undergoing a gynecologic or urologic procedure under general endotracheal anesthesia were enrolled. Anesthesia was maintained with sevoflurane in O2/air, delivered via a Zeus or FLOW-i workstation (14 patients each). Every fifteen min, FGF was changed to randomly selected values ranging from 0.2 to 6 L/min while the sevoflurane vaporizer setting was left at the discretion of the anesthesiologist. The FETsevo was collected every min for 1 h. For each patient, a Gas Man® simulation was run using patient weight and the same FGF, vaporizer and minute ventilation settings used during the procedure. For cardiac output, the Gas Man default setting was used (= Brody formula). Gas Man®'s performance was assessed by comparing measured with Gas Man® predicted FETsevo using linear regression and Varvel's criteria [median performance error (MDPE), median absolute performance error (MDAPE), and divergence]. Additional analysis included separating performance for the wash-in (0-15 min) and maintenance phase (15-60 min). For the FLOW-i, MDPE, MDAPE and divergence were 1% [- 6, 8], 7% [3, 15] and - 0.96%/h [- 1.14, - 0.88], respectively. During the first 15 min, MDPE and MDAPE were 18% [1, 51] and 21% [8, 51], respectively, and during the last 45 min 0% [- 7, 5] and 6% [2, 10], respectively. For the Zeus, MDPE, MDAPE and divergence were 0% [- 5, 8], 6% [3, 12] and - 0.57%/h [- 0.85, - 0.16], respectively. During the first 15 min, MDPE and MDAPE were 7% [- 6, 28] and 13% [6, 32], respectively, and during the last 45 min - 1% [- 5, 5] and 5% [2, 9], respectively. In conclusion, Gas Man® predicts FETsevo in O2/air in adults over a wide range of FGF and vaporizer settings using different workstations with both MDPE and MDAPE < 10% during the first hour of anesthesia, with better relative performance for simulating maintenance than wash-in. In the authors' opinion, this degree of performance suffices for Gas Man® to be used to quantify the environmental impact of FGF reduction in real life practice of the wash-in and maintenance period combined.

Memsorb™, a novel CO2 removal device part II: in vivo performance with the Zeus IE®.

Memsorb™ (DMF Medical, Halifax, Canada) is a novel device based upon membrane oxygenator technology designed to eliminate CO2 from exhaled gas when using a circle anesthesia circuit. Exhaled gases pass through semipermeable hollow fibers and sweep gas flowing through these fibers creates a diffusion gradient for CO2 removal. In vivo Memsorb™ performance was tested during target-controlled closed-circuit anesthesia (TCCCA) with desflurane in O2/air using a Zeus IE® anesthesia workstation (Dräger, Lübeck, Germany). Clinical care protocols for using this novel device were guided by in vitro performance results from a prior study (submitted simultaneously). After IRB approval, written informed consent was obtained from 10 ASA PS I-III patients undergoing robot-assisted radical prostatectomy. TCCCA targets were 39% inspired O2 concentration (FIO2) and 5.0% end-expired desflurane concentration (FETdes). Minute ventilation (MV) was adjusted to maintain 4.5-6.0% FETCO2. The O2/air (40% O2) sweep flow into the Memsorb™ was manually adjusted in an attempt to keep inspired CO2 concentration (FICO2) ≤ 0.8%. The following data were collected: FIO2, FETdes, FICO2, FETCO2, MV, fresh gas flow (FGF, O2 and air), sweep flow, and cumulative desflurane usage (Vdes). Vdes of the Zeus IE®-Memsorb™ combination was compared with historical Vdes observed in a previous study when soda lime (DrägerSorb 800 +) was used. Results are reported as median and inter-quartiles. A combination of manually adjusting sweep flow (26 [21,27] L/min) and MV sufficed to maintain FICO2 ≤ 0.8% and FETCO2 ≤ 6.0%, except in one patient in whom the target Zeus IE® FGF had to be increased to 0.7 L/min for 6 min. FIO2 and FETdes were maintained close to their targets. Zeus IE® FGF after 5 min was 0 [0,0] mL/min. Average Vdes after 50 min was higher with Memsorb™ (20.3 mL) compared to historical soda lime canister data (12.3 mL). During target-controlled closed-circuit anesthesia in patients undergoing robot-assisted radical prostatectomy, the Memsorb™ maintained FICO2 ≤ 0.8% and FETCO2 ≤ 6.0%, and FIO2 remained close to target. Modest amounts of desflurane were lost with the use of the Memsorb™. The need for adjustments of sweep flow, minute ventilation, and occasionally Zeus IE® FGF indicates that the Memsorb™ system should preferentially be integrated into an automated closed-loop system.

Memsorb™, a novel CO2 removal device part I: in vitro performance with the Zeus IE®.

Soda lime-based CO2 absorbents are safe, but not ideal for reasons of ecology, economy, and dust formation. The Memsorb™ is a novel CO2 removal device that uses cardiopulmonary bypass oxygenator technology instead: a sweep gas passes through semipermeable hollow fibers, adding or removing gas from the circle breathing system. We studied the in vitro performance of a prototype Memsorb™ used with a Zeus IE® anesthesia machine when administering sevoflurane and desflurane in O2/air mixtures. The Zeus IE® equipped with Memsorb™ ventilated a 2L breathing bag with a CO2 inflow port in its tip. CO2 kinetics were studied by using different combinations of CO2 inflow (VCO2), Memsorb™ sweep gas flow, and Zeus IE® fresh gas flow (FGF) and ventilator settings. More specifically, it was determined under what circumstances the inspired CO2 concentration (FICO2) could be kept < 0.5%. O2 kinetics were studied by measuring the inspired O2 concentration (FIO2) resulting from different combinations of Memsorb™ sweep gas flow and O2 concentrations, and Zeus IE® FGFs and O2 concentrations. Memsorb™'s sevoflurane and desflurane waste was determined by measuring their injection rates during target-controlled closed-circuit anesthesia (TCCCA), and were compared to historical controls when using a soda lime absorbent (Draegersorb 800+) under identical conditions. With 160 mL/min VCO2 and 5 L/min minute ventilation (MV), lowering the sweep gas flow at any fixed Zeus IE® FGF increased FICO2 in a non-linear manner. Sweep gas flow adjustments kept FICO2 < 0.5% over the entire Zeus IE® FGF range tested with VCO2 up to 280 mL/min; tidal volume and respiratory rate affected the required sweep gas flow. At 10 L/min MV and low FGF (< 1.5 L/min), even a maximum sweep flow of 43 L/min was unable to keep FICO2 ≤ 0.5%. When the O2 concentration in the Zeus IE® FGF and the Memsorb™ sweep gas flow differed, FIO2 drifted towards the sweep gas O2 concentration, and more so as FGF was lowered; this effect was absent once FGF > minute ventilation. During sevoflurane and desflurane TCCCA, the Zeus IE® FGF remained zero while agent usage per % end-expired agent increased with increasing end-expired target agent concentrations and with a higher target FIO2. Agent waste during target-controlled delivery was higher with Memsorb™ than with the soda lime product, with the difference remaining almost constant over the FGF range studied. With a 5 L/min MV, Memsorb™ successfully removes CO2 with inflow rates up to 240 mL/min if an FICO2 of 0.5% is accepted, but at 10 L/min MV and low FGF (< 1.5 L/min), even a maximum sweep flow of 43 L/min was unable to keep FICO2 ≤ 0.5%. To avoid FIO2 deviating substantially from the O2 concentration in the fresh gas, the O2 concentration in the fresh gas and sweep gas should match. Compared to the use of Ca(OH)2 based CO2 absorbent, inhaled agent waste is increased. The device is most likely to find its use integrated in closed loop systems.

Carbon Dioxide Absorption During Inhalation Anesthesia: A Modern Practice.

CO2 absorbents were introduced into anesthesia practice in 1924 and are essential when using a circle system to minimize waste by reducing fresh gas flow to allow exhaled anesthetic agents to be rebreathed. For many years, absorbent formulations consisted of calcium hydroxide combined with strong bases like sodium and potassium hydroxide. When Sevoflurane and Desflurane were introduced, the potential for toxicity (compound A and CO, respectively) due to the interaction of these agents with absorbents became apparent. Studies demonstrated that strong bases added to calcium hydroxide were the cause of the toxicity, but that by eliminating potassium hydroxide and reducing the concentration of sodium hydroxide to <2%, compound A and CO production is no longer a concern. As a result, CO2 absorbents have been developed that contain little or no sodium hydroxide. These CO2 absorbent formulations can be used safely to minimize anesthetic waste by reducing fresh gas flow to approach closed-circuit conditions. Although absorbent formulations have been improved, practices persist that result in unnecessary waste of both anesthetic agents and absorbents. While CO2 absorbents may seem like a commodity item, differences in CO2 absorbent formulations can translate into significant performance differences, and the choice of absorbent should not be based on unit price alone. A modern practice of inhalation anesthesia utilizing a circle system to greatest effect requires reducing fresh gas flow to approach closed-circuit conditions, thoughtful selection of CO2 absorbent, and changing absorbents based on inspired CO2.

Symptom monitoring in cancer and fully automated advice on supportive care: Patients' perspectives on self-management strategies and the eHealth self-management application Oncokompas.

OBJECTIVE: The web-based application Oncokompas was developed to support cancer patients to self-manage their symptoms. This qualitative study was conducted to obtain insight in patients' self-management strategies to cope with cancer and their experiences with Oncokompas as a fully automated behavioural intervention technology. METHODS: Data were collected from semi-structured interviews with 22 participants (10 head and neck cancer survivors and 12 incurably ill patients). Interview questions were about self-management strategies and experiences with Oncokompas. Interviews were audio-recorded, transcribed verbatim and analysed using thematic analysis. RESULTS: Participants applied several self-management strategies, among which trying to stay in control and make the best of their situation. They described Oncokompas' added value: being able to monitor symptoms and having access to a personal online library. Main reasons for not using Oncokompas were concentration problems, lack of time or having technical issues. Recommendations were made for further development of Oncokompas, relating to its content, technical and functional aspects. CONCLUSIONS: Survivors and incurably ill patients use various self-management strategies to cope with cancer. The objectives of self-management interventions as Oncokompas correspond well with these strategies: taking a certain responsibility for your well-being and being in charge of your life as long as possible by obtaining automated information (24/7) on symptoms and tailored supportive care options.

End-tidal to Arterial Gradients and Alveolar Deadspace for Anesthetic Agents.

BACKGROUND: According to the "three-compartment" model of ventilation-perfusion ((Equation is included in full-text article.)) inequality, increased (Equation is included in full-text article.)scatter in the lung under general anesthesia is reflected in increased alveolar deadspace fraction (VDA/VA) customarily measured using end-tidal to arterial (A-a) partial pressure gradients for carbon dioxide. A-a gradients for anesthetic agents such as isoflurane are also significant but have been shown to be inconsistent with those for carbon dioxide under the three-compartment theory. The authors hypothesized that three-compartment VDA/VA calculated using partial pressures of four inhalational agents (VDA/VAG) is different from that calculated using carbon dioxide (VDA/VACO2) measurements, but similar to predictions from multicompartment models of physiologically realistic "log-normal" (Equation is included in full-text article.)distributions. METHODS: In an observational study, inspired, end-tidal, arterial, and mixed venous partial pressures of halothane, isoflurane, sevoflurane, or desflurane were measured simultaneously with carbon dioxide in 52 cardiac surgery patients at two centers. VDA/VA was calculated from three-compartment model theory and compared for all gases. Ideal alveolar (PAG) and end-capillary partial pressure (Pc'G) of each agent, theoretically identical, were also calculated from end-tidal and arterial partial pressures adjusted for deadspace and venous admixture. RESULTS: Calculated VDA/VAG was larger (mean ± SD) for halothane (0.47 ± 0.08), isoflurane (0.55 ± 0.09), sevoflurane (0.61 ± 0.10), and desflurane (0.65 ± 0.07) than VDA/VACO2 (0.23 ± 0.07 overall), increasing with lower blood solubility (slope [Cis], -0.096 [-0.133 to -0.059], P < 0.001). There was a significant difference between calculated ideal PAG and Pc'G median [interquartile range], PAG 5.1 [3.7, 8.9] versus Pc'G 4.0[2.5, 6.2], P = 0.011, for all agents combined. The slope of the relationship to solubility was predicted by the log-normal lung model, but with a lower magnitude relative to calculated VDA/VAG. CONCLUSIONS: Alveolar deadspace for anesthetic agents is much larger than for carbon dioxide and related to blood solubility. Unlike the three-compartment model, multicompartment (Equation is included in full-text article.)scatter models explain this from physiologically realistic gas uptake distributions, but suggest a residual factor other than solubility, potentially diffusion limitation, contributes to deadspace.

Estimating the Impact of Carbon Dioxide Absorbent Performance Differences on Absorbent Cost During Low-Flow Anesthesia.

BACKGROUND: Reducing fresh gas flow when using a circle anesthesia circuit is the most effective strategy for reducing both inhaled anesthetic vapor cost and waste. As fresh gas flow is reduced, the amount of exhaled gas rebreathed increases, but the utilization of carbon dioxide absorbent increases as well. Reducing fresh gas flow may not make economic sense if the increased cost of absorbent utilization exceeds the reduced cost of anesthetic vapor. The primary objective of this study was to determine the minimum fresh gas flow at which absorbent costs do not exceed vapor savings. Another objective is to provide a qualitative insight into the factors that influence absorbent performance as fresh gas flow is reduced. METHODS: A mathematical model was developed to compare the vapor savings with the cost of carbon dioxide absorbent as a function of fresh gas flow. Parameters of the model include patient size, unit cost of vapor and carbon dioxide absorbent, and absorbent capacity and efficiency. Boundaries for fresh gas flow were based on oxygen consumption or a closed-circuit condition at the low end and minute ventilation to approximate an open-circuit condition at the high end. Carbon dioxide production was estimated from oxygen consumption assuming a respiratory quotient of 0.8. RESULTS: For desflurane, the cost of carbon dioxide absorbent did not exceed vapor savings until fresh gas flow was almost equal to closed-circuit conditions. For sevoflurane, as fresh gas flow is reduced, absorbent costs increase more slowly than vapor costs decrease so that total costs are still minimized for a closed circuit. Due to the low cost of isoflurane, even with the most effective absorbent, the rate of absorbent costs increase more rapidly than vapor savings as fresh gas flow is reduced, so that an open circuit is least expensive. The total cost of vapor and absorbent is still lowest for isoflurane when compared with the other agents. CONCLUSIONS: The relative costs of anesthetic vapor and carbon dioxide absorbent as fresh gas flow is reduced are dependent on choice of anesthetic vapor and performance of the carbon dioxide absorbent. Absorbent performance is determined by the product selected and strategy for replacement. Clinicians can maximize the performance of absorbents by replacing them based on the appearance of inspired carbon dioxide rather than the indicator. Even though absorbent costs exceed vapor savings as fresh gas flow is reduced, isoflurane is still the lowest cost choice for the environmentally sound practice of closed-circuit anesthesia.

Ten years of the Helsinki Declaration on patient safety in anaesthesiology: An expert opinion on peri-operative safety aspects.

: Patient safety is an activity to mitigate preventable patient harm that may occur during the delivery of medical care. The European Board of Anaesthesiology (EBA)/European Union of Medical Specialists had previously published safety recommendations on minimal monitoring and postanaesthesia care, but with the growing public and professional interest it was decided to produce a much more encompassing document. The EBA and the European Society of Anaesthesiology (ESA) published a consensus on what needs to be done/achieved for improvement of peri-operative patient safety. During the Euroanaesthesia meeting in Helsinki/Finland in 2010, this vision was presented to anaesthesiologists, patients, industry and others involved in health care as the 'Helsinki Declaration on Patient Safety in Anaesthesiology'. In May/June 2020, ESA and EBA are celebrating the 10th anniversary of the Helsinki Declaration on Patient Safety in Anaesthesiology; a good opportunity to look back and forward evaluating what was achieved in the recent 10 years, and what needs to be done in the upcoming years. The Patient Safety and Quality Committee (PSQC) of ESA invited experts in their fields to contribute, and these experts addressed their topic in different ways; there are classical, narrative reviews, more systematic reviews, political statements, personal opinions and also original data presentation. With this publication we hope to further stimulate implementation of the Helsinki Declaration on Patient Safety in Anaesthesiology, as well as initiating relevant research in the future.

End of year summary 2019: anaesthesia and airway management.

This end of the year summary reviews anesthesia related manuscripts that have been published in the Journal of Clinical Monitoring and Computing in 2019. Anesthesia is currently defined as being composed of unconsciousness, immobility, and autonomic nervous system (ANS) control (Br J Anaesth;122:e127-e135135, Egan 2019). Pain is a postoperative issue, because by definition unconsciousness implies pain cannot be experienced. We first review work related to these aspect of the profession: unconsciousness (EEG, target control), immobility (muscle relaxants), and ANS control. Regaining consciousness has to be accompanied by pain control, and it is important to ensure that the patient regains baseline cognitive function. Anesthesia machine equipment, drug administration, and airway related topics make up the rest of published manuscripts.

European Society of Anaesthesiology Task Force on Nitrous Oxide: a narrative review of its role in clinical practice.

Nitrous oxide (N2O) is one of the oldest drugs still in use in medicine. Despite its superior pharmacokinetic properties, controversy remains over its continued use in clinical practice, reflecting in part significant improvements in the pharmacology of other anaesthetic agents and developing awareness of its shortcomings. This narrative review describes current knowledge regarding the clinical use of N2O based on a systematic and critical analysis of the available scientific literature. The pharmacological properties of N2O are reviewed in detail along with current evidence for the indications and contraindications of this drug in specific settings, both in perioperative care and in procedural sedation. Novel potential applications for N2O for the prevention or treatment of chronic pain and depression are also discussed. In view of the available evidence, we recommend that the supply of N2O in hospitals be maintained while encouraging its economic delivery using modern low flow delivery systems. Future research into its potential novel applications in prevention or treatment of chronic conditions should be pursued to better identify its role place in the developing era of precision medicine.

The effect of isocapnic hyperventilation on early recovery after remifentanil/sevoflurane anesthesia in O2 /air: A randomized trial.

BACKGROUND: Isocapnic hyperventilation (ICHV) may hasten emergence from general anesthesia but remains inadequately studied. We prospectively determined emergence time after sevoflurane anesthesia of variable duration with and without ICHV. METHODS: In 25 ASA I-II patients, general anesthesia was maintained with one age-adjusted MAC sevoflurane in O2 /air and target-controlled remifentanil delivery. At the start of skin closure, the remifentanil effect-site concentration was reduced to 1.5 ng/mL, any residual neuromuscular block reversed, and once the remifentanil effect-site concentration had decreased to 1.5 ng/mL, remifentanil and sevoflurane administration was stopped, and the fresh gas flow increased above minute ventilation. Patients randomly received either normoventilation (n = 13) or ICHV (doubling minute ventilation while titrating CO2 into the inspiratory limb to maintain isocapnia [n = 12]). Three early recovery end points were determined: time to proper response to verbal command; time to extubation; and time to stating one's name. RESULTS: Demographics were the same in both groups. Recovery end points were reached faster in the ICHV group compared to the normoventilation group: time to proper response to verbal command was 7.6 ± 2.2 vs 9.9 ± 2.9 min (P = 0.03); time to extubation was 7.6 ± 2.6 vs 11.0 ± 2.4 min (P = 0.002); and time to stating one's name was 8.9 ± 2.8 vs 12.5 ± 2.6 min (P = 0.003). Within each group, duration of anesthesia only marginally affected the times to reach these recovery end points. CONCLUSION: Isocapnic hyperventilation only had a small effect on emergence times after anesthesia, suggesting that isocapnic hyperventilation may have limited clinical benefits with modern potent inhaled anesthetics.

EOY summary 2018.

Clinical monitoring and technology are at the heart of anesthesiology, and new technological developments will help to define how anesthesiology will evolve as a profession. Anesthesia related research published in the JCMC in 2018 mainly pertained to ICU sedation with inhaled agents, anesthesia workstation technology, and monitoring of different aspects of depth of anesthesia.