Arterial and Mixed Venous Kinetics of Desflurane and Sevoflurane, Administered Simultaneously, at Three Different Global Ventilation to Perfusion Ratios in Piglets with Normal Lungs.

BACKGROUND: Previous studies have established the role of various tissue compartments in the kinetics of inhaled anesthetic uptake and elimination. The role of normal lungs in inhaled anesthetic kinetics is less understood. In juvenile pigs with normal lungs, the authors measured desflurane and sevoflurane washin and washout kinetics at three different ratios of alveolar minute ventilation to cardiac output value. The main hypothesis was that the ventilation/perfusion ratio (VA/Q) of normal lungs influences the kinetics of inhaled anesthetics. METHODS: Seven healthy pigs were anesthetized with intravenous anesthetics and mechanically ventilated. Each animal was studied under three different VA/Q conditions: normal, low, and high. For each VA/Q condition, desflurane and sevoflurane were administered at a constant, subanesthetic inspired partial pressure (0.15 volume% for sevoflurane and 0.5 volume% for desflurane) for 45 min. Pulmonary arterial and systemic arterial blood samples were collected at eight time points during uptake, and then at these same times during elimination, for measurement of desflurane and sevoflurane partial pressures. The authors also assessed the effect of VA/Q on paired differences in arterial and mixed venous partial pressures. RESULTS: For desflurane washin, the scaled arterial partial pressure differences between 5 and 0 min were 0.70 ± 0.10, 0.93 ± 0.08, and 0.82 ± 0.07 for the low, normal, and high VA/Q conditions (means, 95% CI). Equivalent measurements for sevoflurane were 0.55 ± 0.06, 0.77 ± 0.04, and 0.75 ± 0.08. For desflurane washout, the scaled arterial partial pressure differences between 0 and 5 min were 0.76 ± 0.04, 0.88 ± 0.02, and 0.92 ± 0.01 for the low, normal, and high VA/Q conditions. Equivalent measurements for sevoflurane were 0.79 ± 0.05, 0.85 ± 0.03, and 0.90 ± 0.03. CONCLUSIONS: Kinetics of inhaled anesthetic washin and washout are substantially altered by changes in the global VA/Q ratio for normal lungs.

Effects of different plasma target concentrations of remifentanil on the MACBAR of sevoflurane in children with laparoscopic surgery.

BACKGROUND: To investigate the effects of different plasma target concentrations of remifentanil on the minimum alveolar concentration (MAC) for blocking adrenergic response (BAR) of sevoflurane in children with laparoscopic herniorrhaphy. METHODS: Seventy-five children with 3-7 years old scheduled for laparoscopic herniorrhaphy were randomly divided into group R0, group R1, and group R2 according to different remifentanil plasma target concentration (0, 1, and 2 ngml-1), respectively. The MACBAR of sevoflurane was determined by the up-and-down and sequential method in each group. The concentrations of epinephrine and noradrenaline were also determined at corresponding time points. RESULTS: A total of 52 child patients were used among the anticipated 75 patients. In groups R0, R1, and R2, the MACBAR of sevoflurane was (3.29 ± 0.17) %, (2.12 ± 0.10) % and (1.29 ± 0.11) %, respectively, and a significant difference was found among the three groups (P<0.05). The changes of epinephrine and noradrenaline concentrations in each group before and after insufflation of carbon dioxide pneumoperitoneum showed no significant differences. CONCLUSION: Remifentanil by target-controlled infusion can effectively reduce the MACBAR of sevoflurane during laparoscopic surgery in children. At a similar effect of MACBAR, both the changes of epinephrine and noradrenaline concentrations are not affected by the infusion of different remifentanil target concentrations. TRIAL REGISTRATION: The trial was registered at http://www.chictr.org.cn ( ChiCTR1800019393 , 8, Nov, 2018).

Effects of different remifentanil target concentrations on MACBAR of sevoflurane in patients with liver dysfunction under carbon dioxide pneumoperitoneum stimulus: A randomized controlled trial.

WHAT IS KNOWN AND OBJECTIVE: Remifentanil can effectively decrease the sevoflurane concentration to block sympathetic adrenergic response to CO2 pneumoperitoneum stimulus,and liver dysfunction will significantly reduce the MACBAR (minimum alveolar concentration for blocking adrenergic response) of sevoflurane. However, the effects of different remifentanil concentrations on the MACBAR of sevoflurane in patients with liver dysfunction are unclear. The aim of this study was to observe the effects of different remifentanil concentrations by intravenous target-controlled infusion on the MACBAR of sevoflurane in patients with grade B liver dysfunction under carbon dioxide pneumoperitoneum stimulus. METHODS: Seventy-five patients with grade B liver dysfunction undergoing elective laparoscopic surgery were selected, and randomly divided into three groups with remifentanil plasma target concentrations of 0 (group R0 ), 1 (group R1 ) and 2 (group R2 ) ng/ml. Anaesthesia was induced by intravenous injection of propofol 2-3 mg/kg, remifentanil 2 µg/kg and cisatracurium 0.15 mg/kg. All groups were inhaled different concentrations of sevoflurane. The determination of sevoflurane MACBAR in each group was used a method of sequential-allocation technique, and venous blood samples were taken before and after the creation of carbon dioxide pneumoperitoneum to determine plasma adrenaline and noradrenaline concentrations. RESULTS AND DISCUSSIONS: The MACBAR of sevoflurane in groups R0 , R1 and R2 was 4.83%, 3.00% and 2.10%, respectively. The MACBAR of sevoflurane was significantly difference among the three groups. When a similar effect of MACBAR had achieved in each group, no significant differences were found in the changes of plasma adrenaline and noradrenaline concentrations before and after the creation of pneumoperitoneum. What is new and conclusion Target-controlled infusion of different concentrations of remifentanil can reduce sevoflurane MACBAR during pneumoperitoneum stimulation in patients with liver dysfunction in some degree. However, the changes of plasma adrenaline and noradrenaline concentrations are consistent in the three groups when patient's stress response was inhibited at the same degree.

Intravenous versus Volatile Anesthetic Effects on Postoperative Cognition in Elderly Patients Undergoing Laparoscopic Abdominal Surgery.

BACKGROUND: Delayed neurocognitive recovery after surgery is associated with poor outcome. Most surgeries require general anesthesia, of which sevoflurane and propofol are the most commonly used inhalational and intravenous anesthetics. The authors tested the primary hypothesis that patients with laparoscopic abdominal surgery under propofol-based anesthesia have a lower incidence of delayed neurocognitive recovery than patients under sevoflurane-based anesthesia. A second hypothesis is that there were blood biomarkers for predicting delayed neurocognitive recovery to occur. METHODS: A randomized, double-blind, parallel, controlled study was performed at four hospitals in China. Elderly patients (60 yr and older) undergoing laparoscopic abdominal surgery that was likely longer than 2 h were randomized to a propofol- or sevoflurane-based regimen to maintain general anesthesia. A minimum of 221 patients was planned for each group to detect a one-third decrease in delayed neurocognitive recovery incidence in propofol group compared with sevoflurane group. The primary outcome was delayed neurocognitive recovery incidence 5 to 7 days after surgery. RESULTS: A total of 544 patients were enrolled, with 272 patients in each group. Of these patients, 226 in the propofol group and 221 in the sevoflurane group completed the needed neuropsychological tests for diagnosing delayed neurocognitive recovery, and 46 (20.8%) in the sevoflurane group and 38 (16.8%) in the propofol group met the criteria for delayed neurocognitive recovery (odds ratio, 0.77; 95% CI, 0.48 to 1.24; P = 0.279). A high blood interleukin-6 concentration at 1 h after skin incision was associated with an increased likelihood of delayed neurocognitive recovery (odds ratio, 1.04; 95% CI, 1.01 to 1.07; P = 0.007). Adverse event incidences were similar in both groups. CONCLUSIONS: Anesthetic choice between propofol and sevoflurane did not appear to affect the incidence of delayed neurocognitive recovery 5 to 7 days after laparoscopic abdominal surgery. A high blood interleukin-6 concentration after surgical incision may be an independent risk factor for delayed neurocognitive recovery.

Effect of low-dose ketamine on MACBAR of sevoflurane in laparoscopic cholecystectomy: A randomized controlled trial.

WHAT IS KNOWN AND OBJECTIVE: Low-dose ketamine can reduce the minimum alveolar concentration of sevoflurane necessary to block the adrenergic response (MACBAR ) in animals. However, the effects of low-dose ketamine on the sevoflurane MACBAR in patients undergoing laparoscopic surgery are unclear. The aim of this study was to investigate the effects of three different low doses of ketamine on the MACBAR of sevoflurane in patients undergoing laparoscopic cholecystectomy. METHODS: One hundred patients who underwent laparoscopic cholecystectomy were enrolled. After general anaesthesia induction and tracheal intubation, patients received sevoflurane anaesthesia in combination with a loading dose of saline followed by infusion or a loading dose of 0.5 mg/kg ketamine followed by a continuous infusion of 5 (K1 group), 10 (K2 group) and 20 µg/kg/min (K3 group). The target concentration of end-tidal sevoflurane was maintained for at least 20 minutes before carbon dioxide pneumoperitoneum stimulus. The MACBAR of sevoflurane in each group was determined by using an up-and-down sequential allocation technique. RESULTS AND DISCUSSION: Seventy-one patients completed the study. The values of MACBAR for sevoflurane were 5.3% in the K0 , 4.8% in K1 , 3.3% in K2 and 3.2% in K3 groups. The use of ketamine significantly reduced the MACBAR of sevoflurane compared to sevoflurane alone. The K2 and K3 groups showed significantly lower values of MACBAR than that in the K1 group. However, a higher dose of ketamine in the K3 group did not further reduce the sevoflurane MACBAR . The mean arterial blood pressure (MAP) values before pneumoperitoneum in the K2 and the K3 groups were significantly higher compared to those in the K0 and K1 groups. Compared with the values before pneumoperitoneum, the heart rate and MAP after pneumoperitoneum were significantly increased. Overall, the haemodynamics remained stable during the study period in all groups. WHAT IS NEW AND CONCLUSION: A loading dose of 0.5 mg/kg ketamine followed by a continuous infusion of 10.0 µg/kg/min led to a significant decrease in the MACBAR of sevoflurane in patients undergoing laparoscopic cholecystectomy.

Anesthetic Potency of Intravenous Infusion of 20% Emulsified Sevoflurane and Effect on the Blood-Gas Partition Coefficient in Dogs.

BACKGROUND: Intravenous (IV) infusions of volatile anesthetics in lipid emulsion may increase blood lipid concentration, potentially altering the anesthetic agent's blood solubility and blood-gas partition coefficient (BGPC). We examined the influence of a low-lipid concentration 20% sevoflurane emulsion on BGPC, and the anesthetic potency of this emulsion using dogs. METHODS: We compared BGPC and anesthetic characteristics in 6 dogs between the IV anesthesia of emulsion and the sevoflurane inhalation anesthesia in a randomized crossover substudy. Minimum alveolar concentrations (MACs) were determined by tail-clamp stimulation by using the up-and-down method. Blood sevoflurane concentration and partial pressure were measured by gas chromatography; end-tidal sevoflurane concentration was measured using a gas monitor. The primary outcome was BGPC at the end of IV anesthesia and inhalation anesthesia. Secondary outcomes were time to loss/recovery of palpebral reflex, finish intubation and awakening, MAC, blood concentration/partial pressure at MAC and awakening, correlation between blood partial pressure and gas monitor, and the safety of emulsions. RESULTS: BGPC showed no difference between IV and inhaled anesthesia (0.859 [0.850-0.887] vs 0.813 [0.791-0.901]; P = .313). Induction and emergence from anesthesia were more rapid in IV anesthesia of emulsion than inhalation anesthesia. MAC of emulsion (1.33% [1.11-1.45]) was lower than that of inhalation (2.40% [2.33-2.48]; P = .031), although there was no significant difference in blood concentration. End-tidal sevoflurane concentration could be estimated using gas monitor during IV anesthesia of emulsion. No major complications were observed. CONCLUSIONS: IV anesthesia with emulsion did not increase the BGCP significantly compared to inhalation anesthesia. It was suggested that the anesthetic potency of this emulsion may be equal to or more than that of inhalation.

Human plasma biomarker responses to inhalational general anaesthesia without surgery.

BACKGROUND: Postoperative neurocognitive disorders may arise in part from adverse effects of general anaesthetics on the CNS, especially in older patients or individuals otherwise vulnerable to neurotoxicity because of systemic disease or the presence of pre-existing neuropathology. Previous studies have documented cytokine and injury biomarker responses to surgical procedures that included general anaesthesia, but it is not clear to what degree anaesthetics contribute to these responses. METHODS: We performed a prospective cohort study of 59 healthy volunteers aged 40-80 yr who did not undergo surgery. Plasma markers of neurological injury and inflammation were measured immediately before and 5 h after induction of general anaesthesia with 1 minimum alveolar concentration of sevoflurane. Biomarkers included interleukin-6 (IL-6), tumour necrosis factor alpha (TNF-α), C-reactive protein (CRP), and neural injury (tau, neurofilament light [NF-L], and glial fibrillary acidic protein [GFAP]). RESULTS: Baseline biomarkers were in the normal range, although NF-L and GFAP were elevated as a function of age. At 5 h after induction of anaesthesia, plasma tau, NF-L, and GFAP were significantly decreased relative to baseline. Plasma IL-6 was significantly increased after anaesthesia, but by a biologically insignificant degree (<1 pg ml-1); plasma TNF-α and CRP were unchanged. CONCLUSIONS: Sevoflurane general anaesthesia without surgery, even in older adults, did not provoke an inflammatory state or neuronal injury at a concentration that is detectable by an acute elevation of measured plasma biomarkers in the early hours after exposure. CLINICAL TRIAL REGISTRATION: NCT02275026.

Population Pharmacodynamics of Propofol and Sevoflurane in Healthy Volunteers Using a Clinical Score and the Patient State Index: A Crossover Study.

BACKGROUND: The population pharmacodynamics of propofol and sevoflurane with or without opioids were compared using the endpoints no response to calling the person by name, tolerance to shake and shout, tolerance to tetanic stimulus, and two versions of a processed electroencephalographic measure, the Patient State Index (Patient State Index-1 and Patient State Index-2). METHODS: This is a reanalysis of previously published data. Volunteers received four anesthesia sessions, each with different drug combinations of propofol or sevoflurane, with or without remifentanil. Nonlinear mixed effects modeling was used to study the relationship between drug concentrations, clinical endpoints, and Patient State Index-1 and Patient State Index-2. RESULTS: The C50 values for no response to calling the person by name, tolerance to shake and shout, and tolerance to tetanic stimulation for propofol (µg · ml) and sevoflurane (vol %; relative standard error [%]) were 1.62 (7.00)/0.64 (4.20), 1.85 (6.20)/0.90 (5.00), and 2.82 (15.5)/0.91 (10.0), respectively. The C50 values for Patient State Index-1 and Patient State Index-2 were 1.63 µg · ml (3.7) and 1.22 vol % (3.1) for propofol and sevoflurane. Only for sevoflurane was a significant difference found in the pharmacodynamic model for Patient State Index-2 compared with Patient State Index-1. The pharmacodynamic models for Patient State Index-1 and Patient State Index-2 as a predictor for no response to calling the person by name, tolerance to shake and shout, and tetanic stimulation were indistinguishable, with Patient State Index50 values for propofol and sevoflurane of 46.7 (5.1)/68 (3.0), 41.5 (4.1)/59.2 (3.6), and 29.5 (12.9)/61.1 (8.1), respectively. Post hoc C50 values for propofol and sevoflurane were perfectly correlated (correlation coefficient = 1) for no response to calling the person by name and tolerance to shake and shout. Post hoc C50 and Patient State Index50 values for propofol and sevoflurane for tolerance to tetanic stimulation were independent within an individual (correlation coefficient = 0). CONCLUSIONS: The pharmacodynamics of propofol and sevoflurane were described on both population and individual levels using a clinical score and the Patient State Index. Patient State Index-2 has an improved performance at higher sevoflurane concentrations, and the relationship to probability of responsiveness depends on the drug used but is unaffected for Patient State Index-1 and Patient State Index-2.

Elimination of Intracardiac Shunting Provides Stable Gas Anesthesia in Tortoises.

Inhalant anesthesia is challenging in chelonians due to a great capacity for breath-holding and an incomplete separation of the cardiac ventricle. Deoxygenated blood can recirculate back into systemic circulation by bypassing the lung in a process referred to as intracardiac right to left (R-L) shunting. Via electrocardiogram gated magnetic resonance imaging, a novel modality to investigate arterial flows in reptiles, intracardiac shunting and its elimination via atropine during gas anesthesia in tortoises (Chelonoidis carbonaria) was demonstrated. The great vessels of the heart were visualized confirming that after shunt-elimination, the flow (mean ± sd) in the pulmonary arteries increased significantly (54.6 ± 9.5 mL min-1 kg-1 vs 10.8 ± 3.4 mL min-1 kg-1; P < 0.008). Consequently, animals required significantly lower concentrations of inhaled anesthetics to maintain a stable anesthesia. To that end, the minimum anesthetic concentration (MAC) of isoflurane needed to maintain surgical anesthesia was measured. A significantly lower MAC was found after administration of atropine (mean MAC ± sd 2.2 ± 0.3% vs 3.2 ± 0.4%; P < 0.002). Previously, MAC has been indeterminable in chelonians likely due to intracardiac shunting, so this report constitutes the first MAC study performed in a tortoise.

Xenon detection in human blood: Analytical validation by accuracy profile and identification of critical storage parameters.

Xenon is a rare, mostly inert, noble gas that has applications in a wide range of fields, including medicine. Xenon acts on the human body as a useful organ-protective and anesthetic agent and has also been previously studied for potential applications in fields such as optics, aerospace and medical imaging. Recently, it was discovered that xenon can boost erythropoietin production, and it has been used as a performance-enhancing agent in international sports competitions such as the Sochi Olympic Games. Therefore, screening methods to detect the misuse of xenon by analysis of biological samples and to monitor anesthesia kinetics and efficiency are being investigated. The aim of this study was to develop and validate an analytical method to detect xenon in blood samples using gas chromatography coupled to tandem mass spectrometry (GC-MS/MS). Preliminary studies were conducted to determine the best parameters for chromatography and mass spectrometry for xenon. The analysis was performed using the multiple reaction monitoring (MRM) mode using the transitions m/z 129 â†’ 129, 131 â†’ 131 for xenon and 84 â†’ 84, 86 â†’ 86 for krypton, which was chosen as the internal standard. The LOD of GC-MS/MS was found to be 52 pmol on-column. Calibration lines and controls were made to obtain an accuracy profile at a range of 2.08-104 nmol with a ß-expectation tolerance interval set at 80% and the acceptability limit set at ±30%. From the accuracy profile, the LOQ of 15 nmol on-column for the range of 2.08-104 nmol was obtained. The method was validated according to the guidelines of the French Society of Pharmaceutical Sciences and Techniques. The detection method was finally validated using blood from test persons subjected to a 15% or 30% xenon mixture with pure oxygen and air for 45 min. Even though the probes were already used for other projects, it was still possible to detect xenon.

Can Mathematical Modeling Explain the Measured Magnitude of the Second Gas Effect?

BACKGROUND: Recent clinical studies suggest that the magnitude of the second gas effect is considerably greater on arterial blood partial pressures of volatile agents than on end-expired partial pressures, and a significant second gas effect on blood partial pressures of oxygen and volatile agents occurs even at relatively low rates of nitrous oxide uptake. We set out to further investigate the mechanism of this phenomenon with the help of mathematical modeling. METHODS: Log-normal distributions of ventilation and blood flow were generated representing the range of ventilation-perfusion scatter seen in patients during general anesthesia. Mixtures of nominal delivered concentrations of volatile agents (desflurane, isoflurane and diethyl ether) with and without 70% nitrous oxide were mathematically modeled using steady state mass-balance principles, and the magnitude of the second gas effect calculated as an augmentation ratio for the volatile agent, defined as the partial pressure in the presence to that in the absence of nitrous oxide. RESULTS: Increasing the degree of mismatch increased the second gas effect in blood. Simultaneously, the second gas effect decreased in the gas phase. The increase in blood was greatest for the least soluble gas, desflurane, and least for the most soluble gas, diethyl ether, while opposite results applied in the gas phase. CONCLUSIONS: Modeling of ventilation-perfusion inhomogeneity confirms that the second gas effect is greater in blood than in expired gas. Gas-based minimum alveolar concentration readings may therefore underestimate the depth of anesthesia during nitrous oxide anesthesia with volatile agents. The effect on minimum alveolar concentration is likely to be most pronounced for the less soluble volatile agents in current use.

Sevoflurane Affects Oxidative Stress and Alters Apoptosis Status in Children and Cultured Neural Stem Cells.

Anesthesia-induced neurotoxicity in immature animals has raised concerns about similar effects occurring in young children. Our study investigated two commonly used anesthetics-sevoflurane and propofol-for neurotoxicity in young children. Forty-seven children (aged 12-36 months) undergoing hypospadias repair surgery were randomized to receive sevoflurane (SG, n = 24) or propofol (PG, n = 23) general anesthesia. Venous blood was collected at three different times-immediately after induction, 2 h, and 3 days after surgery. The cellular portion was assessed for antioxidant defense and DNA damage, using enzyme assay kits and qRT-PCR, respectively, while serum was used to treat cultured neural stem cells (NSCs). MTT assay and TUNEL staining were performed, and the mRNA levels of antioxidant enzymes and apoptosis indicators were evaluated by qRT-PCR. Antioxidant defense and apoptosis status in the SG group were significantly higher than in the PG group at 2 h after surgery. Additionally, exposure of NSCs to postoperative serum of the SG group resulted in decreased cell density and viability, increased TUNEL-positive cells, elevated mRNA levels of antioxidant enzymes, and cleaved caspase-3 expression. Our data shows for the first time that in young children, administration of sevoflurane, but not propofol, leads to temporally increased antioxidant defense and apoptosis status as well as damage of NSCs.

Dynamic thiol disulphide homeostasis in operating theater personnel exposed to anesthetic gases.

BACKGROUND: The purpose of this study was to investigate the association between dynamic thiol/disulphide homeostasis and occupational exposure to volatile anesthetic gases in operating theater personnel. Decreased blood thiol levels and raised blood disulphide levels serve as biomarkers of oxidative stress. METHODS: We included 65 subjects occupationally exposed and 55 unexposed healthy medical professionals into the study. A novel method enabled separate measurements of components involved in dynamic thiol/disulphide homeostasis (native thiol, disulphide, and total thiol). To control for the potential confounding effect on oxidative stress of psychological symptoms potentially caused by occupational stress, we used scores obtained from four different anxiety and depression inventories. RESULTS: Mean ± standard deviation native thiol was found to be 433.35 ± 30.68 in the exposed group, lower than among controls, 446.61 ± 27.8 (P = 0.02). Disulphide in the exposed group was 15.78 ± 5.12, higher than among controls, 12.14 ± 5.33 (P < 0.001). After adjusting for anxiety and depression scores, age and gender, native thiol remained lower and disulphide higher in the exposed group (P = 0.008 and P < 0.001). CONCLUSION: Dynamic thiol/disulphide homeostasis in workers exposed to anesthetic gases was found to be disturbed after adjusting for the possible contribution of anxiety. We infer that this is due to the oxidative effect of exposure to anesthetic gases.

Effect of Bronchoconstriction-induced Ventilation-Perfusion Mismatch on Uptake and Elimination of Isoflurane and Desflurane.

BACKGROUND: Increasing numbers of patients with obstructive lung diseases need anesthesia for surgery. These conditions are associated with pulmonary ventilation/perfusion (VA/Q) mismatch affecting kinetics of volatile anesthetics. Pure shunt might delay uptake of less soluble anesthetic agents but other forms of VA/Q scatter have not yet been examined. Volatile anesthetics with higher blood solubility would be less affected by VA/Q mismatch. We therefore compared uptake and elimination of higher soluble isoflurane and less soluble desflurane in a piglet model. METHODS: Juvenile piglets (26.7 ± 1.5 kg) received either isoflurane (n = 7) or desflurane (n = 7). Arterial and mixed venous blood samples were obtained during wash-in and wash-out of volatile anesthetics before and during bronchoconstriction by methacholine inhalation (100 µg/ml). Total uptake and elimination were calculated based on partial pressure measurements by micropore membrane inlet mass spectrometry and literature-derived partition coefficients and assumed end-expired to arterial gradients to be negligible. VA/Q distribution was assessed by the multiple inert gas elimination technique. RESULTS: Before methacholine inhalation, isoflurane arterial partial pressures reached 90% of final plateau within 16 min and decreased to 10% after 28 min. By methacholine nebulization, arterial uptake and elimination delayed to 35 and 44 min. Desflurane needed 4 min during wash-in and 6 min during wash-out, but with bronchoconstriction 90% of both uptake and elimination was reached within 15 min. CONCLUSIONS: Inhaled methacholine induced bronchoconstriction and inhomogeneous VA/Q distribution. Solubility of inhalational anesthetics significantly influenced pharmacokinetics: higher soluble isoflurane is less affected than fairly insoluble desflurane, indicating different uptake and elimination during bronchoconstriction.

Coronary Sinus Isoflurane Concentration in Cardiac Surgery.

OBJECTIVE: Volatile anesthetic agents such as isoflurane may be associated with fewer adverse myocardial events compared with total intravenous anesthesia in cardiac surgery. The authors aimed to determine whether reasonable isoflurane concentrations at tissue level were being achieved to protect the myocardium using this agent. The isoflurane concentration in myocardium has never been measured. The primary aim was to sample coronary sinus (CS) blood and measure its isoflurane concentration. Secondary aims were to determine whether the CS blood concentration would equilibrate with the arterial blood concentration and the relationship of CS blood concentration with oxygenator exhaust isoflurane concentrations during cardiopulmonary bypass (CPB). DESIGN: Prospective, observational study. SETTING: Single-center university hospital. PARTICIPANTS: The study comprised 23 patients undergoing cardiac surgery using CPB and isoflurane. MEASUREMENTS AND MAIN RESULTS: Shortly after initiation of CPB and insertion of a CS retrograde cardioplegia catheter but before aortic cross-clamping, CS blood was aspirated, followed by radial artery blood, which then were analyzed for isoflurane with gas chromatography and mass spectrometry. The oxygenator exhaust isoflurane level was measured with an anesthetic gas analyzer. The mean arterial and CS isoflurane concentrations were 87.7 ± 50.1 and 73.0 ± 42.9 µg/mL, respectively. There was a significant mean difference of 14.7 µg/mL (95% confidence interval 6.7-22.8) between CS and arterial isoflurane concentrations. Oxygenator exhaust isoflurane levels were correlated positively with those in the CS blood (r = 0.68, p < 0.001) and arterial blood (r = 0.72, p < 0.001). CONCLUSIONS: This was the first study in which CS blood was sampled and measured for isoflurane concentration. The CS isoflurane concentration could be estimated from the isoflurane concentration in the oxygenator exhaust gas. However, the value of this relationship is limited because the CS isoflurane concentration does not accurately represent its myocardial levels during CPB.

Feasibility of Anesthesia Maintenance With Sevoflurane During Cardiopulmonary Bypass: A Pilot Pharmacokinetics Study.

OBJECTIVE: Adequate maintenance of hypnosis during anesthesia throughout surgery using sevoflurane alone was investigated. In addition, sevoflurane pharmacokinetics during cardiopulmonary bypass were analyzed. DESIGN: This was a pilot pharmacokinetic study. SETTING: Tertiary care university hospital. PARTICIPANTS: The study comprised 10 patients aged between 18 and 75 years who underwent elective mitral valve surgery. INTERVENTIONS: The end-tidal and sevoflurane plasma concentrations were measured throughout cardiac surgery procedures involving cardiopulmonary bypass. The sevoflurane plasma concentration was measured using gas chromatography. In addition, the ratio between sevoflurane alveolar concentration and inspired concentration over time (FA/FI) was analyzed to describe wash-in and wash-out curves. MEASUREMENTS AND MAIN RESULTS: Hypnosis was maintained adequately throughout surgery using sevoflurane alone. The bispectral index was maintained between 40 and 60 during cardiopulmonary bypass. The end-tidal sevoflurane was significantly different before and during cardiopulmonary bypass (1.86%±0.54% v 1.30%±0.58%, respectively; p<0.001). However, the sevoflurane plasma concentration was not significantly different before and after cardiopulmonary bypass start-up (40.55 µg/mL [76.62-125.33] before cardiopulmonary bypass and 36.24 µg/mL [56.49-81-42] during cardiopulmonary bypass). This mismatch possibly can be explained by changes that occured after cardiopulmonary bypass start-up, such as reductions of body temperature (36.33°C±0.46°C v 32.98°C±2.38°C, respectively; p<0.001) and hematocrit (35.62%±3.98% v 25.5%±3.08%, respectively; p<0.001). The sevoflurane alveolar concentration varied according to sevoflurane plasma concentration and bispectral index values. No adverse events regarding sevoflurane administration during cardiopulmonary bypass were observed. CONCLUSIONS: Sevoflurane end-tidal values were reliable indicators of adequate anesthesia during all cardiac surgery procedures involving cardiopulmonary bypass.

Xenon elimination kinetics following brief exposure.

Xenon is a modern inhalative anaesthetic with a very low solubility in tissues providing rapid elimination and weaning from anaesthesia. Besides its anaesthetic properties, Xenon promotes the endogenous erythropoietin biosynthesis and thus has been enlisted as prohibited substance by the World Anti-Doping Agency (WADA). For effective doping controls, knowledge about the elimination kinetics of Xenon and the duration of traceability are of particular importance. Seventy-seven full blood samples were obtained from 7 normal weight patients undergoing routine Xenon-based general anaesthesia with a targeted inspiratory concentration of 60% Xenon in oxygen. Samples were taken before and during Xenon inhalation as well as one, two, 4, 8, 16, 24, 32, 40, and 48 h after exposure. Xenon concentrations were assessed in full blood by gas chromatography and triple quadrupole tandem mass spectrometry with a detection limit of 0.25 µmol/L. The elimination of Xenon was characterized by linear regression of log-transformed Xenon blood concentrations, as well as non-linear regression. Xenon exposure yielded maximum concentrations in arterial blood of 1.3 [1.1; 1.6] mmol/L. Xenon was traceable for 24 to 48 h. The elimination profile was characterized by a biphasic pattern with a rapid alpha phase, followed by a slower beta phase showing a first order kinetics (c[Xe] = 69.1e-0.26x , R2 = 0.83, t1/2 = 2.7 h). Time in hours after exposure could be estimated by 50*ln(1.39/c[Xe]0.077 ). Xenon's elimination kinetics is biphasic with a delayed beta phase following a first order kinetics. Xenon can reliably be detected for at least 24 h after brief exposure. Copyright © 2016 John Wiley & Sons, Ltd.

The decrease of NMDAR subunit expression and NMDAR EPSC in hippocampus by neonatal exposure to desflurane in mice.

Desflurane is one of the third generation inhaled anesthetics and can be used in obstetric and pediatric medicine. However, effects of exposure to desflurane on neonatal brain are largely unknown. In this work, 6-day-old C57BL/6J mice were exposed to 1MAC or 1.5MAC desflurane for 2h. When the mice were 28-day-old, the open-field, spontaneous alternation Y-maze and fear conditioning tests were performed to evaluate general activity, working memory and long term memory, respectively. Levels of NMDAR subunits NR1, NR2A, and NR2B expression in hippocampus were evaluated by western blot. NMDAR-mediated excitatory postsynaptic current (EPSC) in mouse hippocampal slice was recorded by whole-cell patch clamp record. Mice exposed to 1.5MAC desflurane had significantly impaired working memory and fear conditioning memory. The protein expression of NMDAR subunits (NR1, NR2B) and NMDAR-mediated EPSC in hippocampus were significantly decreased. However no significant difference was detected between mice exposed to 1.0MAC desflurane and control mice. In conclusion, in an animal model, 6-day-old mice exposed to 1.5MAC desflurane have significant impairments in working memory and contextual fear memory at postnatal day 28, and the decrease of NMDAR subunits expression and NMDAR EPSC in hippocampus may be involved in this process.

Blood lipid abnormality changes the rate of alveolar-capillary uptake of sevoflurane: a prospective, non-interventional, clinical study
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OBJECTIVE: This research studied the influence of different blood lipid components on the rate of alveolar-capillary uptake of sevoflurane. Method: 104 patients aged 20 - 50 years undergoing elective operations under general anesthesia were mechanically ventilated through endotracheal intubation after intravenous injections of midazolam, vecuronium, fentanyl, and etomidate. They inhaled 2% sevoflurane at an oxygen flow of 2 L/min, then the inspired concentrations (FI) and expired concentrations (FA of sevoflurane were recorded at 1, 3, 5, 7, 10, 15, 20, and 30 minutes. These cases were divided into a normal group and an abnormal group according to the lipid levels. Then, based on the lipid criteria, those cases with abnormal lipid levels were classified into a high-triglyceride (TG) and total-cholesterol (TC) group (group TG+TC) and a group with decreased high-density lipoprotein cholesterol (group HDL-C).The values of FA/FI and the times required to reach the titration value FA/FI = 0.8 were calculated were calculated for each group. RESULTS: Compared with the normal group, FA/FI decreased within 7 - 10 minutes (p < 0.05) and the time taken to reach the titration value was prolonged in the abnormal group (p < 0.05). The value of FA/FI decreased during 7 - 10 minutes (p < 0.05) and the time taken to reach the titration value was longer (p < 0.05) in the group TG+TC. CONCLUSIONS: The increased value of blood/gas partition coefficients (B/G) was caused by the increase in the concentrations of TG and TC in blood lipids.
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Sevoflurane and Isoflurane-Pharmacokinetics, Hemodynamic Stability, and Cardioprotective Effects During Cardiopulmonary Bypass.

OBJECTIVES: This study aimed to evaluate the pharmacokinetic profiles of sevoflurane and isoflurane during use of minimized extracorporeal circulation to perform coronary artery bypass graft surgery. Furthermore, cardiovascular stability during bypass and the postoperative release of troponins were evaluated. DESIGN: Prospective, randomized study. SETTING: University hospital. PARTICIPANTS: The study comprised 31 adult patients undergoing coronary artery bypass grafting. INTERVENTIONS: The pharmacokinetic measurements of the concentration of the volatile anesthetics in the arterial and venous blood, air inlet, air outlet, and gas exhaust of the extracorporeal circulation were recorded. Secondary end-points were cardiovascular stability during bypass, amount of postoperative release of troponin, time to extubation, time to discharge from the intensive care unit and the hospital, and 30-day mortality. MEASUREMENTS AND MAIN RESULTS: Thirty patients completed the protocol. The pharmacokinetics of isoflurane and sevoflurane were almost identical, with a rapid wash-in (time to reach 50% of arterial steady state) concentration of 0.87±0.97 minutes and 1.14±0.35 minutes for isoflurane and sevoflurane, respectively, and a biphasic venous elimination with a terminal half-life of approximately 10 minutes for both compounds. There was a correlation between the gas inlet and the gas exhaust of the extracorporeal circulation. No difference in cardiovascular stability was found. High-sensitivity troponin concentrations on the first postoperative morning were 0.355±0.312 µg/mL and 0.225±0.111 µg/mL in the isoflurane and sevoflurane groups, respectively (p = 0.147). CONCLUSIONS: The study found similar pharmacokinetics regarding wash-in and wash-out for sevoflurane and isoflurane. In addition, no difference in cardiovascular stability was found. The markers of cardiac damage were not different between the two anesthetics. Based on these data, sevoflurane and isoflurane might be used equivalently in patients undergoing coronary artery bypass graft surgery with extracorporeal circulation.