High Concentrations Of Sevoflurane Research Articles

Topographical Features of Pediatric Electroencephalography during High Initial Concentration Sevoflurane for Inhalational Induction of Anesthesia.

High-density electroencephalographic (EEG) monitoring remains underutilized in clinical anesthesia, despite its obvious utility in unraveling the profound physiologic impact of these agents on central nervous system functioning. In school-aged children, the routine practice of rapid induction with high concentrations of inspiratory sevoflurane is commonplace, given its favorable efficacy and tolerance profile. However, few studies investigate topographic EEG during the critical timepoint coinciding with loss of responsiveness-a key moment for anesthesiologists in their everyday practice. The authors hypothesized that high initial sevoflurane inhalation would better precipitate changes in brain regions due to inhomogeneities in maturation across three different age groups compared with gradual stepwise paradigms utilized by other investigators. Knowledge of these changes may inform strategies for agent titration in everyday clinical settings. A total of 37 healthy children aged 5 to 10 yr underwent induction with 4% or greater sevoflurane in high-flow oxygen. Perturbations in anesthetic state were investigated in 23 of these children using 64-channel EEG with the Hjorth Laplacian referencing scheme. Topographical maps illustrated absolute, relative, and total band power across three age groups: 5 to 6 yr (n = 7), 7 to 8 yr (n = 8), and 9 to 10 yr (n = 8). Spectral analysis revealed a large shift in total power driven by increased delta oscillations. Well-described topographic patterns of anesthesia, e.g., frontal predominance, paradoxical beta excitation, and increased slow activity, were evident in the topographic maps. However, there were no statistically significant age-related changes in spectral power observed in a midline electrode subset between the groups when responsiveness was lost compared to the resting state. High initial concentration sevoflurane induction causes large-scale topographic effects on the pediatric EEG. Within the minute after unresponsiveness, this dosage may perturb EEG activity in children to an extent where age-related differences are not discernible.

Epileptiform EEG discharges during sevoflurane anesthesia in children: A meta-analysis

ObjectiveTo investigate the overall incidence and associated factors of epileptiform discharges in children during sevoflurane anesthesia. MethodsOur group systematically searched the PubMed, Cochrane library (Central) and EMBASE for the relevant trials from their inception until September 2020. The primary endpoint was the incidence of epileptiform discharges during sevoflurane induction. The secondary endpoints were the incidence of different types of epileptiform discharges, factors associated with these epileptiform events, and other adverse events such as seizure-like movements. ResultsAfter screening of 713 records, eleven studies involving 448 participants were included into the final analysis. Meta-analysis indicated that the overall incidence of Epileptiform EEG discharges was 38.1% (95%confidence interval [CI], 19.1%-59.2%) during sevoflurane anesthesia in children. Subgroup analysis showed that the incidence of these EEG patters was lower when participants were inducted by using the low initial concentration of sevoflurane, compared with the high initial concentration sevoflurane (1.7%, 95%CI, 0.0% to 8.4% versus 47.7%, 95%CI, 25.5% to 70.3%, P < 0.05). The longer exposure (>3 min) of high concentration sevoflurane during induction showed higher rate of epileptiform discharges than a shorter exposure (≤3 min) (48.4%, 95%CI, 20.1% to 77.3% versus 5.7%, 95%CI, 0.00% to 23.5%; P < 0.05). No significant difference for the incidence of epileptiform discharges was observed in subgroup analysis of addition of nitrous oxide (69.2%, 95%CI, 34.0% to 95.7% versus 41.3%, 95%CI, 15.6% to 69.7%, P﹥0.05) and type of EEG monitoring (26.9%, 95%CI, 3.8% to 60.7% versus 53.1%, 95%CI, 25.4% to 79.8%, P﹥0.05). ConclusionsThe incidence of epileptiform EEG events in children during sevoflurane anesthesia varied from 19.1%-59.2%. The low initial concentration technique and shorter exposure time of high concentration sevoflurane may be associated with a decreased incidence of these epileptiform discharges in EEG. SignificanceEpileptiform EEG discharges during sevoflurane anesthesia in children should arouse clinicians’ attention. The use of low initial concentration technique and shorter exposure time of high concentration sevoflurane may be associated with a lower occurrence of these paradoxical events.

Effects of isoflurane and sevoflurane alone and in combination with butorphanol or medetomidine on the bispectral index in chickens

BackgroundThe bispectral index (BIS) is an anaesthesia monitoring technique able to assess the level of central nervous system depression in humans and various animal species. In birds, it has been validated in chickens undergoing isoflurane anaesthesia. The aim of this study was to evaluate in an avian species the influence of isoflurane and sevoflurane on BIS, each at different minimum anaesthetic concentrations (MAC) multiples, alone or combined with butorphanol or medetomidine. Ten chickens (5 males and 5 females) underwent general anaesthesia with isoflurane or sevoflurane alone, and combined with either intramuscular administration of butorphanol (1 mg/kg) or medetomidine (0.1 mg/kg), in a prospective and cross-over study (i.e., 6 treatments per animal). BIS measurements were compared to heart rate (HR), non-invasive blood pressure (NIBP) and to a visual analogue scale (VAS) of anaesthesia depth.ResultsHR was significantly increased, and both NIBP and VAS were significantly reduced, with higher gas concentrations. NIBP (but not HR or VAS) was additionally affected by the type of gas, being lower at higher concentrations of sevoflurane. Butorphanol had no additional effect, but medetomidine led to differences in HR, NIBP, and in particular a reduction in VAS. With respect to deeper level of hypnosis at higher concentrations and the absence of difference between gases, BIS measurements correlated with all other measures (except with HR, where no significant relationship was found) The difference in BIS before (BISpre) and after stimulation (BISpost) did not remain constant, but increased with increasing MAC multiples, indicating that the BISpost is not suppressed proportionately to the suppression of the BISpre values due to gas concentration. Furthermore, neither butorphanol nor medetomidine affected the BIS.ConclusionsThe difference of degree of central nervous system depression monitored by BIS compared with neuromuscular reflexes monitored by VAS, indicate that BIS records a level of anaesthetic depth different from the one deducted from VAS monitoring alone. BIS provided complementary information such as that medetomidine suppressed spinal reflexes without deepening the hypnotic state. As a consequence, it is concluded that BIS improves the assessment of the level of hypnosis in chickens, improving anaesthesia monitoring and anaesthesia quality in this species.

A pharmacodynamic model of tidal volume and inspiratory sevoflurane concentration in children during spontaneous breathing.

High concentrations of sevoflurane causes respiratory depression, mainly due to the decrease in tidal volume (TV) during spontaneous ventilation. The purpose of this study was to identify clinical variables that affect the relationship between TV and sevoflurane concentration, and to establish a population pharmacodynamic modelling approach to TV and sevoflurane concentration in children. A prospective observational study involving 48 patients (≤ 6 years of age) scheduled to undergo general anesthesia using laryngeal mask airway was performed. When the inspiratory sevoflurane concentration reached 2 vol%, the vaporizer was increased to 4 vol% for 5 min, then sevoflurane was decreased to 2 vol% for 5 min. During the study period, TV, end-tidal carbon dioxide, and sevoflurane concentration were recorded every 30 s. Pharmacodynamic analysis using a sigmoid Emax model was performed to assess the TV-sevoflurane concentration relationship. To collapse hysteresis of the pharmacokinetic and pharmacodynamic relationship, the semicompartmental model was applied which does not require a structural model for equilibration delay causing the hysteresis. TV decreased with increasing inspiratory sevoflurane concentrations. Hysteresis between the TV and sevoflurane concentration was observed and was accounted for when the model was developed. Initial TV and maximal reduction in TV were related to body weight. The γ (a steepness of the concentration-response relation curve) was 8.78 and the keo, (a first-order rate constant determining the equilibrium between the end-tidal sevoflurane concentration and effect site sevoflurane concentration) was 2.27 min-1. Changes in TV were correlated with sevoflurane concentration with spontaneous breathing during sevoflurane anesthesia. The initial and maximal TV were related to body weight, in a pediatric population.

Effects of early postnatal sevoflurane exposure on oligodendrocyte maturation and myelination in cerebral white matter of the rat

General anaesthesia may impose significant neurocognitive risks on the developing brain. As brain injury in preterm neonates has a particular predilection for cerebral white matter, we aimed to evaluate the effects of sevoflurane on oligodendrocyte maturation and myelination in a preterm-equivalent rat model. Two-day-old postnatal (P2) Sprague-Dawley rats were exposed to 3.3 % (approximately 1 minimum alveolar concentration [MAC]) or 4.9 % (approximately 1.5 MAC) sevoflurane for 2 h. Physiologic parameters were measured at the end of sevoflurane anaesthesia. Oligodendrocyte proliferation, maturation, and myelination were evaluated by immunofluorescence with specific markers at different time points. Open field test and Morris water maze tests were performed to access behavior changes from P29 to P36. Arterial blood gases values and blood glucose levels were within the normal physiologic range. As compared to control, 4.9 %, but not 3.3 % sevoflurane disturbed oligodendrocyte maturation at P14, resulting in hypomyelination and axonal damage in cerebral white matter at P28. Rats exposed to 4.9 %, but not 3.3 % sevoflurane showed decreased explorative activity and increased anxiety-like behaviour, as well as learning and memory impairments. Furthermore, 4.9 %, but not 3.3 % sevoflurane inhibited oligodendrocyte proliferation in the developing white matter of the rat brain at 12 h post-anaesthesia, with further evidence of widespread reactive astrogliosis. High concentration of sevoflurane (4.9 %) exposure in early postnatal rats may disrupt oligodendrocyte maturation and myelination. Our study has aimed a spotlight on the need for safe and rational use of analgesics in neonates, especially preterm infants.

Effects of sevoflurane anesthesia on intraoperative high-frequency oscillations in patients with temporal lobe epilepsy

PurposeThis is a cross-sectional study without an unexposed group. We elucidated the effects of sevoflurane anesthesia on high-frequency oscillations (HFOs) to examine the usefulness of assessing intraoperative HFOs. MethodsWe recorded electrocorticography in seven patients with medication-resistant temporal lobe epilepsy (TLE) caused by unilateral hippocampal sclerosis who were seizure-free after temporal lobectomy. We analyzed the number of intraoperative spikes and HFOs on spikes in the epileptogenic parahippocampal gyrus and nonepileptogenic superior temporal gyrus with sevoflurane concentrations of 1.5%, 2.0%, 2.5%, and 3.0%. ResultsThe number of spikes and HFOs in the epileptogenic area significantly increased with an increase in the sevoflurane concentration. In the nonepileptogenic area, spikes and HFOs did not significantly increase with increases in the sevoflurane concentration. However, 2.5% sevoflurane markedly induced spikes and ripples but no fast ripples (FRs) in one patient, and 3.0% sevoflurane induced marked increases in both ripples and FRs in two patients. ConclusionsThe proconvulsant effect of sevoflurane on intraoperative HFOs in patients with TLE depends on the concentration. While HFOs induced by higher sevoflurane concentrations may be a useful biomarker for epileptogenic areas, careful interpretation is also needed because a higher sevoflurane concentration can also induce false-positive HFOs in nonepileptogenic areas.

A Prospective Study of Single Breath Vital Capacity Inhalation Induction with High Concentration of Sevoflurane (Sbvc-Hc) for LMA Insertion in Adults for Short Surgical Cases

Background: Sevoflurane is a new volatile anesthetic agent with rapid induction and recovery. A randomized study was carried to access conditions for LMA insertion using Sevoflurane in 25 ASA I &amp; II patients undergoing short duration surgeries.Subjects and Methods:This prospective study was conducted at Department of Anesthesiology and Critical Care, SVS Medical College and Hospital, Mahabubnagar, Telangana, India. After obtaining the institutional ethics committee and written informed consent from the patients, 25 subjects of either sex were included in this study. Age of the subjects was 18 to 60 years. Patients received injection Fentanyl 1 – 2mcg/kg prior to induction. All patients were pre-oxygenated for 3 min with 100% oxygen using a fresh gas flow of 81/min. All patients received inhalational induction with 8% Sevoflurane and O2 flow at 8 L/min with single vital capacity breathe technique. Loss of verbal contact was considered as the desired endpoint for induction, which was assessed by the response to calling out the patient’s name. Then the time of loss of eyelash reflex and jaw relaxation was assessed by anesthesiologist. After adequate jaw relaxation, LMA insertion was attempted.Results:The mean loss of verbal contact was 65.40±9.67second, while the mean for time for loss of eyelash reflex and jaw relaxation were found to be 81.20±9.39 seconds and 103.20 ±12.07 seconds respectively. The mean time for LMA insertion was 122.00±15.61 and the mean attempts for successful LMA insertion was 1.12±0.33. LMA insertion was easy in 23 cases as against difficult in 2 cases. In 2 cases transient cough and biting were recorded. LMA insertion was excellent and satisfactory in 88.0 and 12 percent. However, the mean heart rate at 5 minute after induction showed a significant fall at 5 minutes after induction. The mean values of SBP, DBP and MAP did not differ significantly at pre and induction. However, a significant decrease in SBP was noticed at 1, 2 and at 5 minutes.Conclusion:Sevoflurane is an smooth inhalation anesthesia with rapid onset with adequate jaw relaxation for insertion of LMA in Adults for short duration surgeries. Sevoflurane has got good hemodynamic profile with lesser complications owing to choice of inhalation agent for insertion of LMA.

A high concentration of sevoflurane induces gasping breaths in mice

The purpose of this study is to compare changes in breathing patterns elicited by hypoxic stress and/or anesthetic stress in mice. Spontaneously breathing anesthetized mice whose tracheae were intubated with a tracheal cannula were challenged with hypoxic stress and/or sevoflurane-induced anesthetic stress while ventilation was measured with a pneumotachograph. When anesthesia was maintained at a light level with inhalation of 2.3 % sevoflurane (0.7 MAC), exposure to severe hypoxic gas (5% O2 in N2) triggered a breathing pattern characterized by gasping respiration. Inhalation of a high concentration of sevoflurane (6.5 %: 2.0 MAC) under hyperoxia elicited the same gasping. Also, the combination of mild hypoxia (inhalation of 10 % O2 in N2) and moderate sevoflurane anesthesia (3.25 %: 1.0 MAC) consistently elicited the same gasping, while mild hypoxic and moderate anesthetic stress alone did not elicit any gasping. These findings suggest that both hypoxia-induced gasping and sevoflurane-induced gasping could be generated by the same intrinsic mechanism within the brainstem.

Online monitoring of end-tidal propofol in balanced anesthesia by anisole assisted positive photoionization ion mobility spectrometer

Online measuring end-tidal propofol concentration during balanced anesthesia is important for anesthetists to learn the patient's anesthesia depth as exhaled propofol concentration is well related to blood propofol concentration. In previous work, exhaled propofol was detected using acetone assisted negative photoionization ion mobility spectrometer, however, the existence of high concentration sevoflurane interfered the response of propofol. In this work, an anisole assisted photoionization ion mobility spectrometer operated in positive mode was developed to sensitively and selectively measure the end-tidal propofol by eliminating the interferences of exhaled humidity and sevoflurane during balanced anesthesia. Anisole molecular ion is stable enough not to go under proton transfer reaction with water presents in the exhaled breath. Hence, the exhaled humidity related peaks were eliminated and only one propofol product ion peak (K0 = 1.50 cm2 V−1 s−1) was observed. The relative standard deviation (RSD) ranging from 0.64%–0.91% showed good repeatability and the quantitative range was 0.2–40 ppbv with a response time of 4 s. Finally, the performance of the proposed method was demonstrated by monitoring end-tidal propofol of balanced anesthetized patients during gastric cancer surgery.

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

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). 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. 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). 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.

Toxicity mechanism of sevoflurane in neural stem cells of rats through DNA methylation.

The present study investigated the influence of sevoflurane on the cytotoxicity of neural stem cells of rats and deoxyribonucleic acid (DNA) methylation, and analyzed the correlation between degree of methylation and neurotoxicity of sevoflurane. Ten healthy Sprague-Dawley rats aged 6–8 weeks were randomly selected. The neural stem cells in the hippocampus of rats were isolated, followed by multiplication culture and induced differentiation. The nerve-related factors were observed and detected under a microscope. Moreover, the neural stem cells were treated with sevoflurane in different concentrations. Three wells were only added with the normal medium as the control group (C0), 3 wells were added with the low-concentration sevoflurane (0.2 g/ml) prepared by the medium as the low-concentration group (C1), 3 wells were added with the moderate-concentration of sevoflurane (0.5 g/ml) as the moderate-concentration group (C2), and 3 wells were added with the high-concentration sevoflurane (1 g/ml) as the high-concentration group (C3). The apoptosis rate was detected and calculated via Cell Counting Kit-8 (CCK-8) assay, the content of genomic DNA methylation in neural stem cells in each group was detected via high-performance liquid chromatography (HPLC), and the distribution of methylation in the chromosome in each group was compared. During the culture, neurospheres were produced, and the expression levels of four neural markers were increased. With the increase of sevoflurane concentration and the prolongation of time, the apoptosis rate of stem cells was increased. The content of methylation in cells treated with sevoflurane in a higher concentration was higher than that in other groups (P<0.05). According to the Pearsons correlation analysis, the content of methylation in neural stem cells was directly proportional to the concentration of sevoflurane. Methylation mostly occurred in the autosome, and the content of methylation in the high-concentration group was higher than those in the moderate-concentration, low-concentration and control groups (P<0.05). In conclusion, the concentration of sevoflurane can affect the degree of methylation in neural stem cells of rats and produce certain cytotoxicity.

EEG profiles during general anesthesia in children: A comparative study between sevoflurane and propofol.

In this prospective study, we describe the electroencephalographic (EEG) profiles in children anesthetized with sevoflurane or propofol. Seventy-three subjects (11years, range 5-18) were included and randomly assigned to two groups according to the anesthetic agent. Anesthesia was performed by target-controlled infusion of propofol (group P) or by sevoflurane inhalation (group S). Steady-state periods were performed at a fixed randomized concentration between 2, 3, 4, 5, and 6μg.ml-1 of propofol in group P and between 1, 2, 3, 4, and 5% of sevoflurane in group S. Remifentanil was continuously administered throughout the study. Clinical data, Bispectral Index (BIS), and raw EEG were continuously recorded. The relationship between BIS and anesthetic concentrations was studied using nonlinear regression. For all steady-state periods, EEG traces were reviewed to assess the presence of epileptoid signs, and spectral analysis of raw EEG was performed. Under propofol, BIS decreased monotonically and EEG slowed down as concentrations increased from 2 to 6μg.ml-1 . Under sevoflurane, BIS decreased from 0% to 4% and paradoxically rose from 4% to 5% of expired concentration: this increase in BIS was associated with the occurrence of fast oscillations and epileptoid signs on the EEG trace. Propofol was associated with more delta waves and burst suppression periods compared to sevoflurane. Under deep anesthesia, the BIS and electroencephalographic profiles differ between propofol and sevoflurane. For high concentrations of sevoflurane, an elevated BIS value may be interpreted as a sign of epileptoid patterns or EEG fast oscillations rather than an insufficient depth of hypnosis.

Sevoflurane addiction due to workplace exposure

Rationale:Anesthesiologists have a well-known increased risk of substance abuse. High-concentration of inhalation anesthetics in exhaled air of operating room personnel is detected. such secondhand exposure produces neurobiological sensitization to the reinforcing effects of inhalation anesthetics.Patient concerns:An addictive young male anesthesiologist who was long-term abuse with sevoflurane after 4 years occupational exposure. A 28-year-old anesthesiologist on duty was found deeply sleep in the locker room and coved his nose with Gauze with high-concentration of sevoflurane. He was found addiction to sevoflurane second time. Several life-threatening incidents occurred including severe aspiration pneumonia. No other addiction was found in his history before he became severely dependent on sevoflurane.Diagnoses:A visual analog scale was employed to assess the severity of craving for sevoflurane and the Benzodiazepine Withdrawal Symptom Scale (BWSQ2)-scale was used to assess sevoflurane withdrawal syndrome(WS).Interventions:First time an opened original sevoflurane container filled with water instead of sevoflurane was handed out for a minute in order to elicit craving and withdrawal symptom in five therapeutic single-sessions. Second time an opened original sevoflurane container filled with sevoflurane instead of water was used as his powerful cur-stimulus and also was handed out for a minute.Outcomes:After professional therapy and continuous surveillance he was rehabilitation and back to work. However, after three weeks he became addiction to sevoflurane again. He showed very sensitive to sevoflurane and switched to other career.Lessons:This case emphasizes that secondhand exposure to inhalation anesthetics may be dangerous and increase the life-threatening professional risk to anesthesiologists, although identification of the responsible factor remains difficult. However, the safety of operating room staff should be aroused wide-spread social concern.

Electrophysiologic evaluation of the visual pathway at different depths of sevoflurane anesthesia in diabetic rats

Our study investigated the changes produced by diabetes on the visual pathway in a Wistar rat model. The impact of diabetes at 10 weeks after intraperitoneal streptozotocin (STZ) injection was evaluated through electrophysiological methods like visual evoked potentials (VEP) and electroretinogram (ERG). VEP and ERG were recorded simultaneously under different sevoflurane anesthetic depths. In all tested concentrations, sevoflurane affected the amplitude and latency of VEP and ERG component elements. With increasing anesthetic depths, sevoflurane increased the latencies of VEP N1, P1 and N2 peaks and ERG a- and b- waves in both control and diabetic animals. On the other hand, the amplitude of VEP showed enhancement in higher concentrations of sevoflurane, contrariwise to the drop of amplitude seen in the ERG. Diabetes additionally increased the latencies of VEP peaks and decreased the N1-P1 amplitude of the VEP when compared to control at the same anesthetic depth. The a- and b- waves were also delayed by diabetes at 10 weeks post-STZ diabetic induction, with the exception of highly profound anesthetic depth in which the result for the b wave were conflicting. We found a reduction in amplitude of the a-b wave in diabetic animals, when ERG was recorded under 6% and 8% sevoflurane concentration. In conclusion, neurophysiological studies like VEP and ERG are useful in the assessment of retinal and optic nerve dysfunctions produced by diabetes, yet considering the alterations that occur during anesthesia if this is used.

Mid-gestational sevoflurane exposure inhibits fetal neural stem cell proliferation and impairs postnatal learning and memory function in a dose-dependent manner

Advancements in fetal intervention procedures have led to increases in the number of pregnant women undergoing general anesthesia during the second trimester—a period characterized by extensive proliferation of fetal neural stem cells (NSCs). However, few studies have investigated the effects of mid-gestational sevoflurane exposure on fetal NSC proliferation or postnatal learning and memory function. In the present study, pregnant rats were randomly assigned to a control group (C group), a low sevoflurane concentration group (2%; L group), a high sevoflurane concentration group (3.5%; H group), a high sevoflurane concentration plus lithium chloride group (H + Li group), and a lithium chloride group (Li group) at gestational day 14. Rats received different concentrations of sevoflurane anesthesia for 2 h. The offspring rats were weaned at 28 days for behavioral testing (i.e., Morris Water Maze [MWM]), and fetal brains or postnatal hippocampal tissues were harvested for immunofluorescence staining, real-time PCR, and Western blotting analyses in order to determine the effect of sevoflurane exposure on NSC proliferation and the Wnt/β-catenin signaling pathway. Our results indicated that maternal exposure to 3.5% sevoflurane (H group) during the mid-gestational period impaired the performance of offspring rats in the MWM test, reduced NSC proliferation, and increased protein levels of fetal glycogen synthase kinase-3 beta (GSK-3β). Such treatment also decreased levels of β-catenin protein, CD44 RNA, and Cyclin D1 RNA relative to those observed in the C group. However, these effects were transiently attenuated by treatment with lithium chloride. Conversely, maternal exposure to 2% sevoflurane (L group) did not influence NSC proliferation or the Wnt signaling pathway. Our results suggest that sevoflurane exposure during the second trimester inhibits fetal NSC proliferation via the Wnt/β-catenin pathway and impairs postnatal learning and memory function in a dose-dependent manner.

High-concentration sevoflurane exposure in mid-gestation induces apoptosis of neural stem cells in rat offspring.

Sevoflurane is the most commonly used volatile anesthetic during pregnancy. The viability of neural stem cells directly affects the development of the brain. However, it is unknown whether the use of sevoflurane during the second trimester affects the survival of fetal neural stem cells. Therefore, in this study, we investigated whether exposure to sevoflurane in mid-gestation induces apoptosis of neural stem cells and behavioral abnormalities. On gestational day 14, pregnant rats were anesthetized with 2% or 3.5% sevoflurane for 2 hours. The offspring were weaned at 28 days and subjected to the Morris water maze test. The brains were harvested to examine neural stem cell apoptosis by immunofluorescence and to measure Nestin and SOX-2 levels by western blot assay at 6, 24 and 48 hours after anesthesia as well as on postnatal day (P) 0, 14 and 28. Vascular endothelial growth factor (VEGF) and phosphoinositide 3-kinase (PI3K)/AKT pathway protein levels in fetal brain at 6 hours after anesthesia were assessed by western blot assay. Exposure to high-concentration (3.5%) sevoflurane during mid-gestation increased escape latency and path length to the platform, and it reduced the average duration spent in the target quadrant and platform crossing times. At 6, 24 and 48 hours after anesthesia and at P0, P14 and P28, the percentage of Nestin/terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL)-positive cells was increased, but Nestin and SOX-2 protein levels were decreased in the hippocampus of the offspring. At 6 hours after anesthesia, VEGF, PI3K and phospho-AKT (p-AKT) levels were decreased in the fetal brain. These changes were not observed in animals given low-concentration (2%) sevoflurane exposure. Together, our findings indicate that exposure to a high concentration of sevoflurane (3.5%) in mid-gestation decreases VEGF, PI3K and p-AKT protein levels and induces neural stem cell apoptosis, thereby causing learning and memory dysfunction in the offspring.

ENDOTRACHEAL INTUBATION WITH SEVOFLURANE IN SURGICAL PEDIATRIC PATIENTS: INCREMENTAL VERSUS HIGH CONCENTRATION INHALATION INDUCTION

Background&#x0D; Sevoflurane is a preferred anesthetic agent for induction and maintenance of pediatric anesthesia. Many studies have been undertaken to show the optimal technique of induction with sevoflurane. In this study we compare the optimal time needed for successful tracheal intubation with immediate high concentration sevoflurane and incremental sevoflurane induction in surgical pediatric patients.&#x0D; Patients and Methods&#x0D; With the approval of the Research Scientific and Ethic Committee of the School of Medicine at Sulaimani University at 18th of May 2011, and the informed written consent from the parents, we studied 100 patients of ASA (American Society of Anesthesiologists) physical status І and II elective pediatric surgical patients aged 2-7 years, patients admitted to Sulaimani Teaching Hospital at the Otorhinolaryngology, Head and Neck Surgical Department, from the first of June 2011 to the first of September 2011. Sevoflurane has been used for induction in children who were scheduled for elective adenotonsillectomy operations. Patients were randomly divided into two equal groups, group 1 (G1) 50 patients, using incremental induction with sevoflurane (1-8 %) in 100% O2, the vapor concentration is increased by 1% every few breaths, and group 2 (G2) 50 patients, using high concentration of sevoflurane for induction, (8%) in 100% O2 from the beginning of induction. Intubation is done when the pupils are miotic and centered, after establishing a good muscle relaxation with no movements in response to laryngoscopy and tracheal intubation. The time from induction to successful tracheal intubation is recorded.&#x0D; Results&#x0D; We have found that the mean time for tracheal tube insertion was shorter in (G2) 208.4 seconds ± 44.5 (SD), than (G1) 265.8 seconds ± 44.4 (SD), and this was statistically significant with a P value of less than 0.001, Vital signs were stable in both groups.&#x0D; Conclusion&#x0D; In healthy pediatric patients undergoing mask induction of general anesthesia with sevoflurane, the induction time can be significantly shortened using a high concentration compared with a conventional, incremental induction method.

Sensitivity to Sevoflurane anesthesia is decreased in mice with a congenital deletion of Guanylyl Cyclase-1 alpha

BackgroundVolatile anesthetics increase levels of the neurotransmitter nitric oxide (NO) and the secondary messenger molecule cyclic guanosine monophosphate (cGMP) in the brain. NO activates the enzyme guanylyl cyclase (GC) to produce cGMP. We hypothesized that the NO-GC-cGMP pathway contributes to anesthesia-induced unconsciousness.MethodsSevoflurane-induced loss and return of righting reflex (LORR and RORR, respectively) were studied in wild-type mice (WT) and in mice congenitally deficient in the GC-1α subunit (GC-1−/− mice). Spatial distributions of GC-1α and the GC-2α subunit in the brain were visualized by in situ hybridization. Brain cGMP levels were measured in WT and GC-1−/− mice after inhaling oxygen with or without 1.2% sevoflurane for 20 min.ResultsHigher concentrations of sevoflurane were required to induce LORR in GC-1−/− mice than in WT mice (1.5 ± 0.1 vs. 1.1 ± 0.2%, respectively, n = 14 and 14, P < 0.0001). Similarly, RORR occurred at higher concentrations of sevoflurane in GC-1−/− mice than in WT mice (1.0 ± 0.1 vs. 0.8 ± 0.1%, respectively, n = 14 and 14, P < 0.0001). Abundant GC-1α and GC-2α mRNA expression was detected in the cerebral cortex, medial habenula, hippocampus, and cerebellum. Inhaling 1.2% sevoflurane for 20 min increased cGMP levels in the brains of WT mice from 2.6 ± 2.0 to 5.5 ± 3.7 pmol/mg protein (n = 13 and 10, respectively, P = 0.0355) but not in GC-1−/− mice.ConclusionCongenital deficiency of GC-1α abolished the ability of sevoflurane anesthesia to increase cGMP levels in the whole brain, and increased the concentration of sevoflurane required to induce LORR. Impaired NO-cGMP signaling raises the threshold for producing sevoflurane-induced unconsciousness in mice.

Sevoflurane at 1.0 MAC together with remifentanil and propofol produces clinically acceptable intubation conditions at the vocal cords: A prospective randomized study.

ObjectiveThe overall intubation conditions after tracheal intubation with remifentanil, propofol, and sevoflurane at 1.0 minimum alveolar concentration (MAC) are worse than with rocuronium at 0.45 mg/kg. Therefore, we compared the intubation conditions and laryngeal morbidity (vocal cord injuries, hoarseness, and sore throat) with sevoflurane at 1.2 and 1.4 MAC versus 1.0 MAC.MethodsIn this prospective clinical trial, 90 patients were randomized to 3 groups: the sevoflurane 1.0, 1.2, and 1.4 MAC groups. At 3 min, tracheal intubation was performed and the patients’ intubation conditions were assessed. The vocal cords were examined for injury by videolaryngoscopy. Additionally, the incidence and severity of laryngeal morbidity were compared between women and men.ResultsAcceptable intubation conditions were seen in 72% of the patients without significant differences between the groups. Overall, vocal cord injuries (oedema) occurred in three (4%) patients. Women reported sore throat more often than men (51% vs. 21%, respectively).ConclusionsIntubation conditions were not improved with higher sevoflurane concentrations. The incidence and severity of sore throat were greater in women than men.Trial registration: ClinicalTrials.Gov: NCT 01896245

Tracheal extubation in deeply anesthetized pediatric patients after tonsillectomy: a comparison of high-concentration sevoflurane alone and low-concentration sevoflurane in combination with dexmedetomidine pre-medication

BackgroundDexmedetomidine can facilitate a smooth extubation process and reduce the requirement of sevoflurane and emergence agitation when administrated perioperatively. We aimed to observe the extubation process and the recovery characteristics in pediatric patients undergoing tonsillectomy while anesthetized with either high-concentration sevoflurane alone or low-concentration sevoflurane combined with pre-medication of single dose of intravenous dexmedetomidine.MethodsSeventy-five patients (ASA I or II, aged 3–7 years) undergoing tonsillectomy were randomized into three equal groups: to receive intravenous saline (Group D0), dexmedetomidine 1 μg/kg (Group D1), or dexmedetomidine 2 μg/kg (Group D2) approximately 10 min before anesthesia. Before the end of surgery, sevoflurane were adjusted to 1.5 times, 1.0 time and 0.8 times the minimal effective concentration in groups D0, D1 and D2, respectively. The sevoflurane concentration for each group was maintained for at least 10 min before the tracheal deep-extubation was performed. The extubation event, recovery characteristics and post-op respiratory complications were recorded.ResultsAll tracheal tubes in three groups were removed successfully during deep anesthesia. Nine patients in Group D0, three patients in Group D1, and two patients in Group D2 required oral airway to maintain a patent airway after extubation. The frequency of oral airway usage in groups D1 and D2 were significantly lower than that in Group D0. The percentages of patients with ED and the requirements of fentanyl in groups D1 and D2 were also significantly lower than those in Group D0. The time from extubation to spontaneous eye opening in Group D2 was longer than that in groups D0 and D1. The times of post-anesthesia care unit discharge in groups D0 and D2 were longer than that in Group D1. No other respiratory complications and vomiting were observed.ConclusionA single dose of intravenous dexmedetomidine as pre-medication in combination with low-concentration sevoflurane at the end of surgery provided safe and smooth deep extubation condition and it also lowered the emergence agitation in sevoflurane-anaesthetized children undergoing tonsillectomy. Preoperative dexmedetomidine at 1 μg/kg did not prolong postoperative recovery time.Trial registrationChinese Clinical Trial Registry (ChiCTR): ChiCTR-IOR-16008423, date of registration: 06 may 2016.