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.

Lidocaine Reduces Sevoflurane Consumption and Improves Recovery Profile in Children Undergoing Major Spine Surgery.

BACKGROUND Intravenous lidocaine administered during surgery improves postoperative outcomes; however, few studies have evaluated the relationship between intravenous lidocaine and volatile anesthetics requirements. This study assessed the effects of lidocaine treatment on sevoflurane consumption and postoperative consciousness disorders in children undergoing major spine surgery. MATERIAL AND METHODS Patients were randomly divided into 2 treatment groups: lidocaine and placebo (control). The lidocaine group received lidocaine as a bolus of 1.5 mg/kg over 30 min, followed by a continuous infusion at 1 mg/kg/h to 6 h after surgery. The following data were assessed: end-tidal sevoflurane concentration required to maintain a bispectral index BIS between 40 and 60, intraoperative blood pressure, heart rate, demand for fentanyl, and consciousness level assessed after surgery using the Richmond Agitation-Sedation Scale. Any treatment-related adverse events were recorded. RESULTS Compared to the control group, lidocaine treatment reduced by 15% the end-tidal sevoflurane concentration required to maintain the intraoperative hemodynamic stability and appropriate level of anesthesia (P=0.0003). There were no intergroup differences in total dose of fentanyl used, average mean arterial pressure, or heart rate measured intraoperatively. The postoperative level of patient consciousness did not differ during the first 6 h between groups. After 9 h, more patients in the control group were still sleepy (P=0.032), and there were fewer perioperative complications in the lidocaine group. CONCLUSIONS Lidocaine treatment decreases sevoflurane consumption and improves recovery profiles in children undergoing major spine surgery.

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.

Comparison of the effect of sevoflurane or propofol anesthesia on the regional cerebral oxygen saturation in patients undergoing carotid endarterectomy: a prospective, randomized controlled study.

BACKGROUND: The monitoring of regional cerebral oxygen saturation (SrO2) using near-infrared spectroscopy is useful method to detect cerebral ischemia during. Sevoflurane and propofol decrease cerebral metabolic rate (CMRO2) in a similar manner, but the effects on the cerebral blood flow (CBF) are different. We hypothesized that the effects of sevoflurane and propofol on SrO2 were different in patients with deficits of CBF. This study compared the effect of sevoflurane and propofol on SrO2 of patients undergoing cerebral endarterectomy (CEA). METHOD: Patients undergoing CEA were randomly assigned to the sevoflurane or propofol group (n = 74). The experiment was preceded in 2 stages based on carotid artery clamping. The first stage was from induction of anaesthesia to immediately before clamping of the carotid artery, and the second stage was until the end of the operation after clamping of the carotid artery. Oxygen saturation (SrO2, SpO2), haemodynamic variables (blood pressure, heart rate), respiratory parameters (end-tidal carbon dioxide tension, inspired oxygen tension), concentration of anesthetics, and anesthesia depth (bispectral index score) were recorded. RESULTS: During stage 1 period (before carotid artery clamping), the mean value of the relative changes in SrO2 was higher (P = 0.033) and the maximal decrease in SrO2 was lower in the sevoflurane group compared with the propofol group (P = 0.019) in the contralateral (normal) site. However, there is no difference in ipsilateral site (affected site). SrO2 decreased after carotid artery clamping and increased after declamping, but the difference was not significant between two groups. Changes in mean arterial blood pressure was lower in sevoflurane group than propofol group after the carotid artery declamping (P = 0.048). CONCLUSION: Propofol-remifentanil anesthesia was comparable with sevoflurane-remifentanil anesthesia in an aspect of preserving the SrO2 in patients undergoing carotid endarterectomy. TRIAL REGISTRATION: Clinical Trials.gov identifier: NCT02609087 , retrospectively registered on November 18, 2015.

Quantitation of sevoflurane in whole blood and aqueous solutions by volatile organic compound sensing.

INTRODUCTION: It is difficult to quantify poorly soluble volatile anesthetics in aqueous solutions; this necessitates the development of alternative prompt methods to analyze the in vivo blood concentrations of anesthetics for the clinical assessment of anesthesia depth. In this study, we demonstrated that the difficulties can be overcome by using volatile organic compound (VOC) sensors, which allow the levels of vaporized VOCs to be quantified in several seconds and obviate the need for conventional techniques such as gas chromatography or nuclear magnetic resonance (NMR). METHODS: The concentrations of a volatile general anesthetic (sevoflurane) in aqueous solutions containing human blood components and rabbit blood were measured using a VOC sensor and those in distilled water and phosphatidylcholine suspension were compared to those determined by NMR. RESULTS: For all aqueous solutions with concentrations of up to 5 mM, the relationship between the VOC content and sevoflurane concentration was represented by a straight line passing through the origin. The concentration of sevoflurane determined by VOC sensing was well correlated with the values obtained by NMR at <1 mM, which is within the clinically relevant concentration levels. DISCUSSION: Considering the results from this study, we can conclude that VOC sensing may be useful for measuring intraoperative blood anesthetic concentrations.

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.