Effect of Global Ventilation to Perfusion Ratio, for Normal Lungs, on Desflurane and Sevoflurane Elimination Kinetics.

BACKGROUND: Kinetics of the uptake of inhaled anesthetics have been well studied, but the kinetics of elimination might be of more practical importance. The objective of the authors' study was to assess the effect of the overall ventilation/perfusion ratio (VA/Q), for normal lungs, on elimination kinetics of desflurane and sevoflurane. METHODS: The authors developed a mathematical model of inhaled anesthetic elimination that explicitly relates the terminal washout time constant to the global lung VA/Q ratio. Assumptions and results of the model were tested with experimental data from a recent study, where desflurane and sevoflurane elimination were observed for three different VA/Q conditions: normal, low, and high. RESULTS: The mathematical model predicts that the global VA/Q ratio, for normal lungs, modifies the time constant for tissue anesthetic washout throughout the entire elimination. For all three VA/Q conditions, the ratio of arterial to mixed venous anesthetic partial pressure Part/Pmv reached a constant value after 5 min of elimination, as predicted by the retention equation. The time constant corrected for incomplete lung clearance was a better predictor of late-stage kinetics than the intrinsic tissue time constant. CONCLUSIONS: In addition to the well-known role of the lungs in the early phases of inhaled anesthetic washout, the lungs play a long-overlooked role in modulating the kinetics of tissue washout during the later stages of inhaled anesthetic elimination. The VA/Q ratio influences the kinetics of desflurane and sevoflurane elimination throughout the entire elimination, with more pronounced slowing of tissue washout at lower VA/Q ratios.

Effects of Volatile Anesthetics on Postoperative Ischemic Stroke Incidence.

Background Preclinical studies suggest that volatile anesthetics decrease infarct volume and improve the outcome of ischemic stroke. This study aims to determine their effect during noncardiac surgery on postoperative ischemic stroke incidence. Methods and Results This was a retrospective cohort study of surgical patients undergoing general anesthesia at 2 tertiary care centers in Boston, MA, between October 2005 and September 2017. Exclusion criteria comprised brain death, age <18 years, cardiac surgery, and missing covariate data. The exposure was defined as median age-adjusted minimum alveolar concentration of all intraoperative measurements of desflurane, sevoflurane, and isoflurane. The primary outcome was postoperative ischemic stroke within 30 days. Among 314 932 patients, 1957 (0.6%) experienced the primary outcome. Higher doses of volatile anesthetics had a protective effect on postoperative ischemic stroke incidence (adjusted odds ratio per 1 minimum alveolar concentration increase 0.49, 95% CI, 0.40-0.59, P<0.001). In Cox proportional hazards regression, the effect was observed for 17 postoperative days (postoperative day 1: hazard ratio (HR), 0.56; 95% CI, 0.48-0.65; versus day 17: HR, 0.85; 95% CI, 0.74-0.99). Volatile anesthetics were also associated with lower stroke severity: Every 1-unit increase in minimum alveolar concentration was associated with a 0.006-unit decrease in the National Institutes of Health Stroke Scale (95% CI, -0.01 to -0.002, P=0.002). The effects were robust throughout various sensitivity analyses including adjustment for anesthesia providers as random effect. Conclusions Among patients undergoing noncardiac surgery, volatile anesthetics showed a dose-dependent protective effect on the incidence and severity of early postoperative ischemic stroke.

Prediction of expiratory desflurane and sevoflurane concentrations in lung-healthy patients utilizing cardiac output and alveolar ventilation matched pharmacokinetic models: A comparative observational study.

ABSTRACT: The Gas Man simulation software provides an opportunity to teach, understand and examine the pharmacokinetics of volatile anesthetics. The primary aim of this study was to investigate the accuracy of a cardiac output and alveolar ventilation matched Gas Man model and to compare its predictive performance with the standard pharmacokinetic model using patient data.Therefore, patient data from volatile anesthesia were successively compared to simulated administration of desflurane and sevoflurane for the standard and a parameter-matched simulation model with modified alveolar ventilation and cardiac output. We calculated the root-mean-square deviation (RMSD) between measured and calculated induction, maintenance and elimination and the expiratory decrement times during emergence and recovery for the standard and the parameter-matched model.During induction, RMSDs for the standard Gas Man simulation model were higher than for the parameter-matched Gas Man simulation model [induction (desflurane), standard: 1.8 (0.4) % Atm, parameter-matched: 0.9 (0.5) % Atm., P = .001; induction (sevoflurane), standard: 1.2 (0.9) % Atm, parameter-matched: 0.4 (0.4) % Atm, P = .029]. During elimination, RMSDs for the standard Gas Man simulation model were higher than for the parameter-matched Gas Man simulation model [elimination (desflurane), standard: 0.7 (0.6) % Atm, parameter-matched: 0.2 (0.2) % Atm, P = .001; elimination (sevoflurane), standard: 0.7 (0.5) % Atm, parameter-matched: 0.2 (0.2) % Atm, P = .008]. The RMSDs during the maintenance of anesthesia and the expiratory decrement times during emergence and recovery showed no significant differences between the patient and simulated data for both simulation models.Gas Man simulation software predicts expiratory concentrations of desflurane and sevoflurane in humans with good accuracy, especially when compared to models for intravenous anesthetics. Enhancing the standard model by ventilation and hemodynamic input variables increases the predictive performance of the simulation model. In most patients and clinical scenarios, the predictive performance of the standard Gas Man simulation model will be high enough to estimate pharmacokinetics of desflurane and sevoflurane with appropriate accuracy.

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.

Effect of One-Lung Ventilation on Blood Sevoflurane and Desflurane Concentrations.

OBJECTIVE: To determine the blood sevoflurane and desflurane concentrations during one-lung ventilation (OLV). DESIGN: Randomized, single-blind study. SETTING: Single university hospital. PARTICIPANTS: The study comprised 24 patients, 35 to 70 years old who were scheduled for either a major abdominal surgery or thoracotomy. INTERVENTIONS: The patients were divided into the following 4 groups: sevoflurane two-lung ventilation (TLV), sevoflurane OLV, desflurane TLV, and desflurane OLV. Vaporizers were set at 1.5% sevoflurane or 6% desflurane. MEASUREMENTS AND MAIN RESULTS: In the TLV groups, blood samples were taken in 10-minute intervals starting 40 minutes after the start of TLV (T1-T9) for blood gas analysis and gas chromatography. In the OLV groups, the first sample was collected at 40 minutes of TLV (T1), and other samples were collected in 10-minute intervals from the start of OLV (T2-T9). Saturation of peripheral oxygen (SpO2), hemodynamic variables, and inspired and end-tidal volatiles were recorded. The fraction uptake of the volatile agents (F) was calculated for each patient at the same time points. The mean arterial sevoflurane concentration in the sevoflurane OLV group at T1 decreased from 40.7 ± 4.4 to 30.2 ± 2.5 µg/mL at T3 (p = 0.014, 26% decrease). In the OLV desflurane group, the mean arterial desflurane concentration at T1 declined from 224.6 ± 44.8 to 159.8 ± 32 µg/mL at T3 (p=0.018, 29% decrease). However, the reduction of sevoflurane concentration compared with that of desflurane at T3 was not statistically significant (p = 0.31). In addition, the fraction uptake of the volatile agents values significantly increased at the start of OLV (p = 0.001). CONCLUSION: An OLV procedure causes a decrease in the both arterial and venous blood concentrations of sevoflurane and desflurane. This reduction is believed to be due to ventilation-perfusion mismatch.

Desflurane usage during anesthesia with and without N2O using FLOW-i Automatic Gas Control with three different wash-in speeds.

AGC® (Automatic Gas Control) is the FLOW-i's automated low flow tool (Maquet, Solna, Sweden) that target controls the inspired O2 (FIO2) and end-expired desflurane concentration (FAdes) while (by design) exponentially decreasing fresh gas flow (FGF) during wash-in to a maintenance default FGF of 300 mL min-1. It also offers a choice of wash-in speeds for the inhaled agents. We examined AGC performance and hypothesized that the use of lower wash-in speeds and N2O both reduce desflurane usage (Vdes). After obtaining IRB approval and patient consent, 78 ASA I-II patients undergoing abdominal surgery were randomly assigned to 1 of 6 groups (n = 13 each), depending on carrier gas (O2/air or O2/N2O) and wash-in speed (AGC speed 2, 4, or 6) of desflurane, resulting in groups air/2, air/4, air/6, N2O/2, N2O/4, and N2O/6. The target for FIO2 was set at 35%, while the FAdes target was selected so that the AGC displayed 1.3 MAC (corrected for the additive affect of N2O if used). AGC was activated upon starting mechanical ventilation. Varvel's criteria were used to describe performance of achieving the targets. Patient demographics, end-expired N2O concentration, MAC, FGF, and Vdes were compared using ANOVA. Data are presented as mean ± standard deviation, except for Varvel's criteria (median ± quartiles). Patient demographics did not differ among the groups. Median performance error was -2-0% for FIO2 and -3-1% for FAdes; median absolute performance error was 1-2% for FIO2 and 0-3% for FAdes. MAC increased faster in N2O groups, but total MAC decreased 0.1-0.25 MAC below that in the O2/air groups after 60 min. The effect of wash-in speed on Vdes faded over time. N2O decreased Vdes by 62%. AGC performance for O2 and desflurane targeting is excellent. After 1 h, the wash-in speeds tested are unlikely to affect desflurane usage. N2O usage decreases Vdes proportionally with its reduction in FAtdes.

Desflurano: propriedades físico-químicas, farmacologia e uso clínico / Desflurane: physicochemical properties, pharmacology and clinical use

JUSTIFICATIVA E OBJETIVOS: Seguindo o desenvolvimento da química nuclear com a síntese dos halogenados desde a década de 50 no século passado, vários agentes foram ensaiados clinicamente e alguns tiveram grande aplicaçäo prática. A busca pelo agente ideal continua. Atualmente estäo em uso clínico o halotano, enflurano, isoflurano, sevoflurano e desflurano. Todos apresentam vantagens e desvantagens. O desflurano é o mais recente destes agentes. O objetivo deste trabalho é descrever as propriedades físico-químicas e farmacológicas do desflurano e relatar a aplicaçäo clínica obtida com o uso deste novo agente. CONTEUDO: As propriedades físico-químicas e as características farmacocinéticas e farmacodinâmicas säo determinantes do uso clínico do desflurano. Tendo ponto de ebuliçäo baixo, volatiliza facilmente nas temperaturas das salas de operaçäo, e sua CAM elevada requer que seja administrado em concentraçöes altas. Entäo, é recomendável o uso de fluxo baixo de gás fresco e vaporizador especial para que sua aplicabilidade clínica seja economicamente viável. Além disto, o uso de um agente coadjuvante, como o óxido nitroso, reduz sua CAM e possibilita ser usado em menores concentraçöes. Sua farmacocinética permite induçäo e regressäo rápida, salientando-se também que tem molécula muito estável, sendo pouquíssimo metabolizado, oferecendo grande tolerabilidade para o organismo humano. Suas repercussöes farmacodinâmicas säo doses-dependentes, semelhantes aos demais agentes inalatórios potentes. CONCLUSÖES: O desflurano representa uma etapa a mais na evoluçäo para se chegar ao anestésico ideal. Suas propriedades físico-químicas lhe conferem características farmacocinéticas bastante desejáveis, que propiciam induçäo (progressäo) e regressäo rápidas e também metabolizaçäo mínima com a mais baixa toxicidade orgânica entre os anestésicos halogenados, e forte estabilidade molecular, inclusive na presença de absorventes de dióxido de carbono. Tomando-se as devidas precauçöes quanto à vaporizaçäo, armazenamento e consumo, o desflurano pode ser usado inclusive em larga escala, sendo economicamente viável