Increasing Concentrations Of Sevoflurane Research Articles

Effects of Neuromuscular Blockages on Entropy Monitoring During Sevoflurane Anesthesia.

BackgroundThere are no data available on the effects of different degrees of neuromuscular blockade on spectral entropy during sevoflurane anesthesia. This study aimed to observe the effects of different degrees of neuromuscular blockade on state and response entropy during sevoflurane anesthesia.Material/MethodsEighty-one female patients were randomized to 9 groups (n=9 per group) according to the concentration of sevoflurane and degree of neuromuscular blockade. Response and state entropy were monitored. The endpoints were: 1) impact of neuromuscular blockade on state entropy and response entropy, and the difference between response entropy and state entropy; and 2) the response of entropy after cutaneous tetanic electrical noxious stimulation to the ulnar nerve under different degrees of neuromuscular blockade and concentrations of sevoflurane.ResultsThese were no significant differences in response entropy or state entropy, or differences between response entropy and state entropy among the groups in the awake state (P>0.05). Without noxious stimulation, sevoflurane concentrations and neuromuscular blockade had no significant effects on response entropy or state entropy, or on the difference between response entropy and state entropy (all P>0.05), but sevoflurane concentrations showed a significant effect on state entropy (P<0.05). After noxious stimulation, sevoflurane concentrations and neuromuscular blockade had significant effects on response entropy and state entropy, and on the difference between response entropy and state entropy.ConclusionsResponse entropy and state entropy decreased with increasing sevoflurane concentration. Neuromuscular blockade did not affect entropy without noxious stimulation. With stimulation, muscle relaxants significantly reduced the changes in entropy, and there were significant effects of neuromuscular blockade and sevoflurane on entropy.

Effects of sevoflurane on expression of heparanase and fascin in lung carcinoma cells of mice

Objective To evaluate the effects of sevoflurane on the expression of heparanase (HPA) and fascin in lung carcinoma cells of mice. Methods Mouse LLC cells were inoculated in the culture plate.After being cultured for 24 h, the cells were equally and randomly divided into 4 groups using a random number table: control group (group CC) , 1% sevoflurane group (group Sev1) , 2% sevoflurane group (group Sev2) , and 3% sevoflurane group (group Sev3) . Cells in Sev1-3 groups were exposed to 1%, 2% and 3% sevoflurane, respectively, for 4 h, while cells in group CC were not exposed to sevoflurane, and all the cells were then cultured for another 24 h in an incubator.The invasion of cells was determined by Transwell invasion assay, and the invaded cells were counted.The migration of cells was determined by wound healing assay, and cell migration rates were calculated.The expression of HPA and fascin in cells was detected by Western blot. Results Compared with group CC, the number of invaded cells and cell migration rates were gradually decreased, and the expression of HPA and fascin was gradually down-regulated with increasing concentrations of sevoflurane in Sev1-3 groups. Conclusion The mechanism through which sevoflurane inhibits the metastasis of mouse lung carcinoma cells is associated with down-regulated expression of HPA and fascin. Key words: Anesthetics, inhalation; Lung neoplasms; Neoplasm metastasis; Heparin lyase; Cell movement

Sevoflurane attenuates stress-enhanced fear learning by regulating hippocampal BDNF expression and Akt/GSK-3β signaling pathway in a rat model of post-traumatic stress disorder.

Post-traumatic stress disorder (PTSD) is a psychiatric disease that may occur after intense psychological trauma or physiological stress. Accumulating evidence suggests that brain-derived neurotrophic factor (BDNF) and the serine/threonine kinase (Akt)/glycogen synthase kinase-3β (GSK-3β) signaling pathway are critically involved in brain plasticity, including hippocampal-dependent learning and memory, while sevoflurane impairs memory processing. Thus, we hypothesized that sevoflurane can suppress fear learning by regulating the expression of BDNF and the Akt/GSK-3β signaling pathway in a rat model of PTSD. Rats were exposed to sevoflurane during or after a 15 foot-shock stressor. Thereafter, rats were subjected to a single foot-shock in a totally different environment. The fear response was recorded in response to the 15 foot-shock and the single foot-shock environments. In another set of experiments, the brain tissue was harvested and subjected to biochemistry studies. Our data suggested that increasing sevoflurane concentrations decreased stress-enhanced fear learning (SEFL) when given during but not after the stressor. Furthermore, administration of lithium chloride (100 mg/kg, intraperitoneally) 30 min before the contextual fear conditioning reversed the inhibitory effect of 0.8 % sevoflurane on SEFL as well as phosphorylated (p)-Akt, p-GSK-3β and BDNF expressions. Our data suggested that increasing sevoflurane administration during but not after the stressor can impair SEFL in a rat model of PTSD, which may be due, at least in part, to the regulation of hippocampal BDNF expression and the Akt/GSK-3β signaling pathway.

Effects of caudal sufentanil supplemented with levobupivacaine on blocking spermatic cord traction response in pediatric orchidopexy

Caudal block is one of the most commonly used anesthetic techniques in subumbilical and genitourinary procedures. However, traditional administration of caudal levobupivacaine was inadequate on blocking peritoneal response during spermatic cord traction. The aim of this study was to evaluate whether the addition of caudal sufentanil to levobupivacaine provided better analgesia for children undergoing orchidopexy. Sixty-two patients, scheduled for right orchidopexy, received caudal block after induction. Group LS (n = 31) received levobupivacaine 0.25% 1 ml/kg plus sufentanil 0.5 μg/kg, and group L (n = 31) received levobupivacaine 0.25% 1 ml/kg only. HR or MAP fluctuation >20% or entropy increase >15% during spermatic cord traction was defined as inadequate anesthesia and was treated with increasing sevoflurane concentration. The number of children who needed sevoflurane rescue was counted, and postoperative side effects and quality of sleep were also recorded. There were no statistically significant differences between the two groups in age, weight, and duration of surgery. Two (6.45%) children in group LS required inspired sevoflurane rescue to block hemodynamic fluctuation during spermatic cord traction, as compared with 12 (38.71%) patients in group L (P < 0.001). At the time of exerting spermatic cord traction, the median HR was, respectively, 134 and 145 (P < 0.001); the corresponding response entropy (RE) and state entropy (SE) was 65 and 54, respectively, in group LS versus 76 and 65 in group L (P < 0.001). In pediatric orchidopexy, the addition of sufentanil to levobupivacaine for caudal blockade offers clinical benefit over levobupivacaine alone in blocking the spermatic cord traction response.

Sevoflurane at 1 MAC provides optimal myocardial protection during off-pump CABG

Objective. We investigated the myocardial protective effect of sevoflurane in patients receiving off-pump coronary artery bypass grafting (OPCABG) and the role of brain natriuretic peptide (BNP). Design. Forty-eight patients receiving elective OPCABG were randomly assigned to a control group, and to 0.75 MAC, 1.0 MAC and 1.5 MAC sevoflurane groups. Blood samples were collected and levels of BNP and cardiac troponin I (cTnI) were measured before anesthesia, and immediately, 24, 48 and 72 h after surgery. Results. Dopamine was necessary to maintain blood pressure in the sevoflurane groups, but not in the control group (p < 0.002). 1.0 MAC sevoflurane significantly decreased post-surgical cTnI levels (p < 0.001). 0.75 MAC had no significant effect, and increasing sevoflurane concentrations to 1.5 MAC caused no further decrease in cTnI concentrations. There was no significant difference in BNP level among the groups (p = 0.227) or between any two groups, although values of BNP showed a significant correlation with cTnI values in control subjects immediately after (r = 0.847) and 24 h after (r = 0.661) surgery. Conclusions. Our results demonstrated that 1.0 MAC and 1.5 MAC sevoflurane can exert a significant myocardial protective effect. BNP cannot be used to predict the myocardial protective effect of sevoflurane in OPCABG.

Saving sevoflurane and hastening emergence from anaesthesia using an anaesthetic-conserving device

This study compared an anaesthetic-conserving device (AnaConDa) and a conventional vaporizer in terms of sevoflurane consumption and emergence from anaesthesia using a total gas flow of 4 l min(-1), with a rebreathing circuit. Twenty-four patients for gastrectomy, aged 30-70 years, were divided into AnaConDa and control groups. Anaesthesia was induced with midazolam, propofol, fentanyl and vecuronium. The total gas flow was fixed at 4 l min(-1) (nitrous oxide 2 l min(-1) and oxygen 2 l min(-1)). Sevoflurane administration was started at 0.5% (vaporizer setting) in the control group and 25 ml h(-1) in the AnaConDa group, then the end-tidal sevoflurane concentration was kept between 0.3 and 0.5% in both groups. Analgesia was obtained with intermittent epidural administration of mepivacaine. The time to first detection of end-tidal sevoflurane, sevoflurane consumption and emergence time were compared between the two groups. The AnaConDa group showed a significantly longer time to first detection of end-tidal sevoflurane (211 +/- 75 vs. 40 +/- 18 s), smaller sevoflurane consumption (12 +/- 3 vs. 42 +/- 9 ml), and shorter emergence time (12 +/- 2 vs. 16 +/- 1 min) than the control group. The AnaConDa could decrease sevoflurane consumption and hasten emergence from anaesthesia, but increasing sevoflurane concentration with AnaConDa at the start of anaesthesia might take longer than that with a conventional vaporizer.

Analysis of depth of anesthesia with Hilbert–Huang spectral entropy

Objective Monitoring the effect of anesthetic drug on the neural system is an ongoing challenge for anesthetists. Several methods based on the electroencephalogram (EEG) have been proposed to estimate the depth of anesthesia (DoA); for instance, the Fourier-based time–frequency balanced spectral entropy as implemented in the Datex-Ohmeda M-Entropy Module. In this paper, a novel method based on Hilbert–Huang transform is proposed to calculate a spectral entropy value, called Hilbert–Huang spectral entropy and is applied to EEG recordings during sevoflurane anesthesia. The dose–response relation of Hilbert–Huang spectral entropy during sevoflurane anesthesia is presented. Methods We analyzed a previously collected set of EEG data, obtained from 14 patients’ during the induction of general anesthesia with sevoflurane. The Hilbert–Huang spectral entropy and the Datex-Ohmeda M-Entropy were applied to the EEG recording. State entropy and response entropy based on the Hilbert–Huang spectral entropy and the Datex-Ohmeda M-Entropy were calculated, respectively. The performance of both methods was assessed by pharmacokinetic/pharmacodynamic modeling and prediction probability. To obtain reliable Hilbert–Huang spectral entropy and Datex-Ohmeda M-Entropy values, a combined preprocessor was applied in advance. Results In the awake state, the baseline variability (as estimated by the coefficient of variation) of the Hilbert–Huang spectral entropy was less than half the variability of the Datex-Ohmeda M-Entropy ( p < 0.001). All entropy values decreased similarly with increasing sevoflurane concentration, as shown by the high correlation between the respective methods ( p < 0.001). However, Hilbert–Huang spectral entropy exhibited greater resistance to noise in the EEG signal; and decreased in a more linear fashion with increasing sevoflurane effect-site concentration, particularly around the point of loss of consciousness. The goodness-of-fit of the pharmacokinetic/pharmacodynamic model and the prediction probability using the state entropy of Hilbert–Huang spectrum ( R 2 = 0.86, P k = 0.84) was significantly better than that using the one of M-Entropy ( R 2 = 0.80, P k = 0.81, p < 0.05); however, the difference between response entropy values was not statistically significant. Conclusion The results from this small dataset suggest that the Hilbert–Huang spectral entropy has a slightly stronger ability to track changes in sevoflurane effect-site concentration than M-Entropy with a stronger noise-resistance. Significance Hilbert–Huang spectral entropy could be incorporated in the design of a new method to estimate the effect of anesthetic drugs on the EEG.

Changes in Electroencephalographic Bicoherence During Sevoflurane Anesthesia Combined with Intravenous Fentanyl

With the introduction of bispectral index (BIS) as a measure of a patient's sedation during general anesthesia, attention has been directed toward bispectral analysis of electroencephalography (EEG). In the present study we evaluated the relationship between EEG bicoherence and sevoflurane concentration. Sixteen ASA physical status I-II patients scheduled for elective abdominal surgery were enrolled in the study. Anesthesia was induced with 5% sevoflurane and maintained with sevoflurane and oxygen (50%). Just before surgery, IV fentanyl (2 microg/kg) was given and then continuously infused (2 microg x kg(-1) x h(-1)). Using software we developed, EEG bicoherence, BIS, and 95% spectral edge frequency (SEF95) were recorded at end-tidal sevoflurane concentrations of 0.5%, 0.8%, 1.1%, 1.4%, 1.7%, 2.0%, and 2.3%. Under light anesthesia, EEG bicoherence values were low. With increasing sevoflurane concentrations, 2 peaks of bicoherence emerged along the diagonal line (f1 = f2). Both the first (at around 4 Hz) and second (at around 10 Hz) grew higher (37.7% +/- 7.5% and 35.1% +/- 9.0%, respectively) as the sevoflurane concentration increased to 1.4%. However, the first peak leveled off whereas the second tended to decrease slightly with further increases in sevoflurane concentration. The BIS value decreased as the sevoflurane concentration increased and leveled off at 1.4% and higher concentrations of sevoflurane. The SEF 95 also decreased as the sevoflurane concentration increased up to 2.3%. Thus the distribution pattern of the two bicoherence peaks is likely to be better than BIS of the anesthetic effect of sevoflurane during surgery.

Pharmacokinetic-Pharmacodynamic Modeling the Hypnotic Effect of Sevoflurane Using the Spectral Entropy of the Electroencephalogram

Spectral entropy is a new electroencephalogram (EEG)-derived parameter that may be used to model the pharmacokinetic-pharmacodynamic (PKPD) effects of general anesthetics. In the present study we sought to derive a PKPD model of the relationship between sevoflurane concentration and spectral entropy of the EEG. We collected spectral entropy data during increasing and decreasing sevoflurane anesthesia from 20 patients. The first cycle consisted of induction and lightening phases with no supplemental medications. An effect-site compartment and inhibitory E(max) model described the relation between sevoflurane concentration and spectral entropy. PKPD parameters were derived from the full cycle and separately from the increasing and decreasing stages. The second anesthetic cycle consisted of a redeepening phase only and included airway manipulation and routinely administered adjunctives. PKPD data obtained from the first cycle were used to predict second cycle entropy changes. There was a consistent relationship between effect-site sevoflurane concentration and spectral entropy (median absolute weighted residual = 11.6%). For complete first-cycle response entropy (mean +/- sd): T1/2 K(eo) = 2.4 +/- 1.5 min, gamma = 5.9 +/- 2.3, EC50 = 1.7 +/- 0.3. We found significant differences between gamma values when the sevoflurane concentration was increasing (61.1 +/- 55.2) compared with the decreasing part of the cycle (5.7 +/- 2.8). Above an effect-site concentration of 3%, spectral entropy of the EEG is unresponsive to further increases in sevoflurane concentration. The effect-compartment inhibitory E(max) model accurately describes the relation between sevoflurane concentration and spectral entropy of the EEG. Spectral entropy decreases with increasing sevoflurane concentrations up to 3%. The steepness of the dose-response curve varies between phases of increasing and decreasing anesthetic concentrations.

Haemodynamic and splanchnic organ blood flow responses during sevoflurane-induced hypotension in dogs

The safety of hypotension induced by sevoflurane and splanchnic organ blood flow remains to be clarified. The aim was to investigate the effects of sevoflurane-induced hypotension on systemic haemodynamics and splanchnic organ blood flows in dogs. Mean arterial pressure was maintained at 60 mmHg by increasing sevoflurane concentrations. The renal, hepatic and pancreatic blood flows were measured by using the hydrogen clearance method. Hypotension induced by sevoflurane resulted in a 50% decrease of mean arterial pressure due to a 30% reduction in systemic vascular resistance associated with a 30% decrease in cardiac index. The mechanisms causing the lower cardiac index were produced by the decreases in heart rate and left ventricular dP/dt(max). Renal, hepatic and pancreatic blood flow were reduced, but the whole-body oxygen consumption did not change during the hypotensive period. The haemodynamic changes induced by sevoflurane were caused by the suppression of arterial baroreflexes and myocardial depression, but splanchnic organ blood flows, though reduced, could provide adequate peripheral perfusion to meet the decrease in oxygen supply.

Sevoflurane potentiates and blocks GABA-induced currents through recombinant alpha1beta2gamma2 GABAA receptors: implications for an enhanced GABAergic transmission.

The gamma-aminobutyric acidA receptor (GABAAR) is a target for anaesthetic agents. We investigated the interactions of sevoflurane with a recombinant GABAAR. Emphasis was on the mechanism of block, as relevant open-channel block by a volatile anaesthetic would possibly explain prolonged GABAergic postsynaptic currents. The effect of sevoflurane on GABA-induced currents through recombinant alpha1beta2gamma2 GABAAR channels was studied (patch clamp; HEK293 cells). GABA 0.01 mM or 1 mM was applied alone or together with sevoflurane (0.05 mM to 5 mM). Currents elicited by GABA 0.01 mM were increased by low sevoflurane concentrations to 183% and decreased by high sevoflurane concentrations (> 1 mM) to 34% (P < 0.05). Ten- to 90%-rise times of the currents were reduced by sevoflurane concentration dependently. At GABA (1 mM), peak currents and 10-90%-rise times decreased with increasing sevoflurane concentrations. A transient current increase was induced by discontinuation of GABA and sevoflurane. Such rebound currents indicate a reversal of an open-channel block by sevoflurane. Sevoflurane (a) increases the apparent affinity of GABA to the GABAAR, as suggested by the decreased current rise times. This explains the enhancement of the currents induced by low GABA concentrations (0.01 mM). Additionally, sevoflurane (b) induces a picrotoxin-like open-channel block at the GABAAR. The reversal of the open-channel block elicits a delayed GABA response. These findings indicate at least two different sites of action of sevoflurane at this receptor that are both important for an enhanced GABAergic synaptic transmission.

Effects of sevoflurane on the middle latency auditory evoked response and the electroencephalographic power spectrum.

We investigated the effects of sevoflurane on the middle latency auditory evoked response (MLR) and the power spectrum of the electroencephalogram (EEG) in 10 elective surgical patients. The MLR and the EEG power spectrum were recorded with a surface electrode placed at the central (Cz) scalp location. End-tidal sevoflurane concentrations of 0%, 0.25%, 0.5%, 0.75%, 1.0%, and 1.5% in 50% nitrous oxide and oxygen were studied. The Na, Pa, and Nb components of the MLR increased in latency and decreased in amplitude in a dose-dependent manner at increasing concentrations of sevoflurane. The latencies for Na, Pa, and Nb increased in a linear fashion (correlation coefficients: r = 0.81, r = 0.81, and r = 0.89, respectively). The EEG delta power was dominant with increasing sevoflurane concentration, and was significantly increased at sevoflurane concentrations of 1.0%-1.5%. The beta power, median power frequency (MPF), and 95% spectral edge frequency (SEF) decreased significantly according to the increases by 0.5% sevoflurane. Regarding the changes evoked by 0.25% sevoflurane, the Nb latency of the MLR responded significantly under 0.75% of sevoflurane. At these low concentrations of sevoflurane, the MLR seemed to be more sensitive to changes in anesthetic concentration than the various EEG variables.

Effects of Sevoflurane on the Middle Latency Auditory Evoked Response and the Electroencephalographic Power Spectrum

We investigated the effects of sevoflurane on the middle latency auditory evoked response (MLR) and the power spectrum of the electroencephalogram (EEG) in 10 elective surgical patients.The MLR and the EEG power spectrum were recorded with a surface electrode placed at the central (Cz) scalp location. End-tidal sevoflurane concentrations of 0%, 0.25%, 0.5%, 0.75%, 1.0%, and 1.5% in 50% nitrous oxide and oxygen were studied. The Na, Pa, and Nb components of the MLR increased in latency and decreased in amplitude in a dose-dependent manner at increasing concentrations of sevoflurane. The latencies for Na, Pa, and Nb increased in a linear fashion (correlation coefficients: r = 0.81, r = 0.81, and r = 0.89, respectively). The EEG delta power was dominant with increasing sevoflurane concentration, and was significantly increased at sevoflurane concentrations of 1.0%-1.5%. The beta power, median power frequency (MPF), and 95% spectral edge frequency (SEF) decreased significantly according to the increases by 0.5% sevoflurane. Regarding the changes evoked by 0.25% sevoflurane, the Nb latency of the MLR responded significantly under 0.75% of sevoflurane. At these low concentrations of sevoflurane, the MLR seemed to be more sensitive to changes in anesthetic concentration than the various EEG variables. (Anesth Analg 1995;80:940-3)