Anesthetic Agent Propofol Research Articles

BSA stabilised AuNCs as a ‘Turn-Off’ fluorescent probe for the sensing of propofol

The abuse of anaesthetic agent propofol is an increasing challenge in worldwide, therefore it is essential to develop simple and accurate methods for its detection. In the present study, a simple turn-off fluorescent sensing platform for the detection of propofol based on bovine serum albumin (BSA) stabilized gold nanoclusters (AuNCs) was developed. The fluorescent BSA-AuNCs were successfully prepared via previously reported microwave assisted method. The prepared red emitting BSA-AuNCs shows emission maximum at 685nm on excitation at 500nm. The fluorescence of the probe was quenched remarkably by the addition of propofol, due to electron transfer mechanism. The limit of detection (LoD) of propofol was found to be 0.12μM. This detection method has good selectivity towards propofol over other co-existing biomolecules and neurotransmitters. Moreover, this method was also utilized for the analysis of propofol spiked real samples (both blood serum & urine) and good recovery percentages were found. A paper strip assay was also successfully conducted for practical application.

Propofol selectively modulates functional connectivity signatures of sustained attention during rest and narrative listening.

Sustained attention is a critical cognitive function reflected in an individual's whole-brain pattern of functional magnetic resonance imaging functional connectivity. However, sustained attention is not a purely static trait. Rather, attention waxes and wanes over time. Do functional brain networks that underlie individual differences in sustained attention also underlie changes in attentional state? To investigate, we replicate the finding that a validated connectome-based model of individual differences in sustained attention tracks pharmacologically induced changes in attentional state. Specifically, preregistered analyses revealed that participants exhibited functional connectivity signatures of stronger attention when awake than when under deep sedation with the anesthetic agent propofol. Furthermore, this effect was relatively selective to the predefined sustained attention networks: propofol administration modulated strength of the sustained attention networks more than it modulated strength of canonical resting-state networks and a network defined to predict fluid intelligence, and the functional connections most affected by propofol sedation overlapped with the sustained attention networks. Thus, propofol modulates functional connectivity signatures of sustained attention within individuals. More broadly, these findings underscore the utility of pharmacological intervention in testing both the generalizability and specificity of network-based models of cognitive function.

Anesthesia Management in Intramural Uterine Myoma and Obesity Morbid Patients Who Underwent Myomectomy Perlaparatomy

Introduction. Obesity is a condition that increases the challenges in the surgical process. Obesity increases the risk of sleep apnea and affects anaesthetics. This case report aims to discuss the management of anaesthesia in a patient with morbid obesity.
 Case. Female, 26 years old, with intramural uterine myoma and morbid obesity, will undergo myomectomy per laparotomy with ASA II physical status, performed anaesthesia with general anaesthesia intubation technique using the anaesthetic agent Propofol 1-2.5 mg/kg titration until the patient falls asleep, fentanyl 1-2 mcg/kg, then the patient was intubated in a ramped position with sleep non-apnea. After it was confirmed that the ETT was entered, 30 mg of a muscle relaxant (atracurium) was added. The operation lasts 1 hour 30 minutes, with a bleeding 250 cc, hemodynamically stable.
 Conclusion. Morbid obesity has extraordinary implications for anaesthetic management. Various considerations for patients with morbid obesity are needed starting from the preoperative, intraoperative, to postoperative periods. Regional anaesthesia is preferred because the physiological function of unhealthy obese patients is impaired due to excess body weight. Selection of anaesthetic agent and calculation of drug dose is crucial to know because there is a change in the volume of distribution. The pharmacokinetics of most general anaesthetics are affected by the adipose tissue mass, produce a prolonged drug effect, and less predictable.

The quantitative EEG in electroencephalogram-based brain monitoring during general anesthesia

Das Elektroenzephalogramm (EEG) findet im klinischen Alltag der Anästhesie des deutschsprachigen Raumes zunehmend Anwendung. Bei über 90 % der Patienten ändert sich das frontale EEG als Reaktion auf die Gabe der gebräuchlichen Narkotika (Propofol und volatile Narkosegase) in typischer Weise. Eine adäquate Narkosetiefe und angemessene Konzentrationen der Anästhetika im Gehirn erzeugen meist frontale Oszillationen zwischen 8 und 12 Hz (α-Oszillationen) sowie langsame δ‑Wellen zwischen 0,5 und 4 Hz. Die frontale EEG-Ableitung eignet sich gut zur Vermeidung einer unzureichenden Narkosetiefe bzw. einer Überdosierung von Anästhetika. Im Folgenden werden die klinische Interpretation der wichtigsten EEG-Muster und ihr biophysikalischer Hintergrund erläutert. Ebenso werden wichtige Limitationen und „Fallstricke“ für den klinischen Alltag diskutiert, die der Anästhesist kennen sollte, um das EEG als zwar unvollständigen, aber klinisch äußerst wichtigen Parameter des Bewusstseinslevels zu nutzen.

Effect of Propofol and Fentanyl on Brain Oxidative Stress after Systemic Lipopolysaccharide Injection in Rats

Systemic inflammation causes brain oxidative stress, a prerequisite for neurodegeneration. In this study, we investigated the effect of the anesthetic agents propofol and fentanyl on brain oxidative stress during mild systemic endotoxemia induced by lipopolysaccharide (LPS) endotoxin. For this purpose, rats were administered LPS (400 μg/kg, intraperitoneally; i.p.), treated at the same time with different doses of propofol or fentanyl, i.p., and euthanized 4 h later. Other groups were treated with the saline, only propofol, or only fentanyl. Oxidative stress markers including malondialdehyde (MDA), nitric oxide (NO), and reduced glutathione (GSH) were determined. In addition, nuclear factor kappaB (NF-kB), paraoxonase-1 (PON-1), and butyrylcholinesterase (BChE) activities were measured in the brain tissue. Results showed that compared with the saline group, administration of LPS caused a marked and significant increase in brain MDA and NO combined with depletion of GSH and decreased PON-1 and BChE activities. Additionally, the active form of NF-kB was significantly increased in the brain of LPS only-treated rats. Treatment with propofol or fentanyl led to a marked and significant decrease in the levels of brain MDA and NO together with a significant increase in GSH and restoration of PON-1 and BChE activities. Furthermore, lower levels of active form of NF-kB were found following treatment with propofol or fentanyl compared with those in the LPS only group. Collectively, these results suggest that propofol and fentanyl exhibit an antioxidant action and attenuate the endotoxin-induced brain oxidative stress.

Comparison of postoperative cognitive dysfunction with the use of propofol versus desflurane in patients undergoing surgery for clipping of aneurysm after subarachnoid hemorrhage.

Background: Cerebral aneurysm rupture is a distinct entity among various causes of cerebrovascular accident. Despite the current concept of early surgical clipping to prevent consequences of ruptured aneurysm in good grade subarachnoid hemorrhage patients, 40–50% have postoperative cognitive dysfunction (POCD) on a long- term basis. Here, we compared the effect of two commonly used anesthetic agents on cognitive function following cerebral aneurysmal surgery, i.e., propofol and desflurane.Methods: We conducted a prospective double-blind clinical study in 70 patients who were randomized to receive maintenance anesthetic agents either propofol or desflurane. The cognitive functions of patients were studied at the time of the discharge from a hospital or at 2 weeks following surgery whichever was early using the Hindi version of the Montreal Cognitive Assessment scale. The hemodynamic parameters, brain relaxation score at the different time intervals, were also studied.Results: There was no difference between the two anesthetic agents in terms of incidence of POCD (65.4% vs. 82.6%, P > 0.05) at the time of discharge or at 2 weeks following surgery. The mean POCD score in propofol and desflurane group was 22.81 ± 4.45 and 19.09 ± 5.66 which was statistically significant (P-value-0.01). The scores for domains of executive function, attention, and orientation were better with propofol group than desflurane group. Intraoperative hemodynamics and brain relaxation scores were similar in both groups.Conclusion: A significant number of patients undergoing aneurysmal neck surgery experienced POCD although incidence remained similar in both groups. However, it appears that mean cognitive score and certain domains of cognitive functions especially the executive function, attention, and orientation were better preserved with the use of propofol when compared to desflurane at the time of discharge or on 2 weeks following surgery whichever was early.

Anesthesia Management in Intramural Uterine Myoma and Obesity Morbid Patients Who Underwent Myomectomy Perlaparatomy

ABSTRACT
 Introduction. Obesity is a condition that increases the challenges in the surgical process. Obesity increases the risk of sleep apnea and affects anaesthetics. This case report aims to discuss the management of anaesthesia in a patient with morbid obesity.
 Case. Female, 26 years old, with intramural uterine myoma and morbid obesity, will undergo myomectomy per laparotomy with ASA II physical status, performed anaesthesia with general anaesthesia intubation technique using the anaesthetic agent Propofol 1-2.5 mg/kg titration until the patient falls asleep, fentanyl 1-2 mcg/kg, then the patient was intubated in a ramped position with sleep non-apnea. After it was confirmed that the ETT was entered, 30 mg of a muscle relaxant (atracurium) was added. The operation lasts 1 hour 30 minutes, with a bleeding 250 cc, hemodynamically stable.Conclusion. Morbid obesity has extraordinary implications for anaesthetic management. Various considerations for patients with morbid obesity are needed starting from the preoperative, intraoperative, to postoperative periods. Regional anaesthesia is preferred because the physiological function of unhealthy obese patients is impaired due to excess body weight. Selection of anaesthetic agent and calculation of drug dose is crucial to know because there is a change in the volume of distribution. The pharmacokinetics of most general anaesthetics are affected by the adipose tissue mass, produce a prolonged drug effect, and less predictable.

Consciousness & Brain Functional Complexity in Propofol Anaesthesia

The brain is possibly the most complex system known to mankind, and its complexity has been called upon to explain the emergence of consciousness. However, complexity has been defined in many ways by multiple different fields: here, we investigate measures of algorithmic and process complexity in both the temporal and topological domains, testing them on functional MRI BOLD signal data obtained from individuals undergoing various levels of sedation with the anaesthetic agent propofol, replicating our results in two separate datasets. We demonstrate that the various measures are differently able to discriminate between levels of sedation, with temporal measures showing higher sensitivity. Further, we show that all measures are strongly related to a single underlying construct explaining most of the variance, as assessed by Principal Component Analysis, which we interpret as a measure of “overall complexity” of our data. This overall complexity was also able to discriminate between levels of sedation and serum concentrations of propofol, supporting the hypothesis that consciousness is related to complexity - independent of how the latter is measured.

Effect of Anesthetic Agents on Cognitive Function and Peripheral Inflammatory Biomarkers in Young Patients Undergoing Surgery for Spine Disorders.

Background:Exposure to anesthesia has been postulated to affect the cognitive function by inciting central nervous system inflammation. Hence, we planned to compare the psychometrical effects of anesthetic agents propofol, desflurane, or sevoflurane on postoperative cognitive function and also measure the change in concentration of serum S-100β, interleukin (IL)-6, and tumor necrosis factor (TNF)-α to look for the contribution of systemic inflammation.Methods:This was a prospective, double-blind, randomized controlled trial. Intuitional ethical committee approval and consent from patients were obtained. We enrolled 66 patients, allocated into three equal groups to receive either sevoflurane (n = 22), desflurane (n = 22), or propofol (n = 22). Standard anesthesia protocol was followed titrated to a bispectral index of 40–60. Patients with preoperative mini-mental state examination ≤23 were excluded. Each patient was assessed thrice with battery of cognitive tests in preoperative period (baseline), after 72 h (early postoperative cognitive dysfunction [POCD]), after 3 months (delayed POCD) of surgery. Serum levels of IL-6, TNF-α, and S-100β were measured preoperatively and 72 h after surgery.Results:Mean scores of various psychometric tests improved slightly in early postoperative period which was not statistically significant (P > 0.5). In delayed postoperative period, there was significant improvement in scores as compared to baseline (P < 0.5) in all the groups. There was nonsignificant change in the levels of biomarkers S-100β, TNF-α, and IL-6 between baseline and postoperative period in all the groups.Conclusion:In young patients, there is no effect of anesthesia on postoperative cognitive functions. There is no association of inflammatory markers with respect to the patient's cognitive status.

Adaptive smith predictor controller for total intravenous anesthesia automation.

Anesthetic agent propofol needs to be administered at an appropriate rate to prevent hypotension and postoperative adverse reactions. To comprehend more suitable anesthetic drug rate during surgery is a crucial aspect. The main objective of this proposal is to design robust automated control system that work efficiently in most of the patients with smooth BIS and minimum variations of propofol during surgery to avoid adverse post reactions and instability of anesthetic parameters. And also, to design advanced computer control system that improves the health of patient with short recovery time and less clinical expenditures. Unlike existing research work, this system administrates propofol as a hypnotic drug to regulate BIS, with fast bolus infusion in induction phase and slow continuous infusion in maintenance phase of anesthesia. The novelty of the paper lies in possibility to simplifythe drug sensitivity-based adaption with infusion delay approach to achieve closed-loop control of hypnosis during surgery. Proposed work uses a brain concentration as a feedback signal in place of the BIS signal. Regression model based estimated sensitivity parameters are used for adaption to avoid BIS signal based frequent adaption procedure and large offset error. Adaptive smith predictor with lead-lag filter approach is applied on 22 different patients' model identified by actual clinical data. The actual BIS and propofol infusion signals recorded during clinical trials were used to estimate patient's sensitivity parameters EC 50 and λ. Simulation results indicate that patient's drug sensitivity parameters based adaptive strategy facilitates optimal controller performance in most of the patients. Results are obtained with proposed scheme having less settling time, BIS oscillations and small offset error leads to adequate depth of anesthesia. A comparison with manual control mode and previously reported system shows that proposed system achieves reduction in the total variations of the propofol dose. Proposed adaptive scheme provides better performance with less oscillation in spite of computation delay, surgical stimulations and patient variability. Proposed scheme also provides improvement in robustness and may be suitable for clinical practices.

Anesthesia modifies subthreshold critical slowing down in a stochastic Hodgkin-Huxley-like model with inhibitory synaptic input.

The dynamics of a stochastic type-I Hodgkin-Huxley-like point neuron model exposed to inhibitory synaptic noise are investigated as a function of distance from spiking threshold and the inhibitory influence of the general anesthetic agent propofol. The model is biologically motivated and includes the effects of intrinsic ion-channel noise via a stochastic differential equation description as well as inhibitory synaptic noise modeled as multiple Poisson-distributed impulse trains with saturating response functions. The effect of propofol on these synapses is incorporated through this drug's principal influence on fast inhibitory neurotransmission mediated by γ-aminobutyric acid (GABA) type-A receptors via reduction of the synaptic response decay rate. As the neuron model approaches spiking threshold from below, we track membrane voltage fluctuation statistics of numerically simulated stochastic trajectories. We find that for a given distance from spiking threshold, increasing the magnitude of anesthetic-induced inhibition is associated with augmented signatures of critical slowing: fluctuation amplitudes and correlation times grow as spectral power is increasingly focused at 0 Hz. Furthermore, as a function of distance from threshold, anesthesia significantly modifies the power-law exponents for variance and correlation time divergences observable in stochastic trajectories. Compared to the inverse square root power-law scaling of these quantities anticipated for the saddle-node bifurcation of type-I neurons in the absence of anesthesia, increasing anesthetic-induced inhibition results in an observable exponent <-0.5 for variance and >-0.5 for correlation time divergences. However, these behaviors eventually break down as distance from threshold goes to zero with both the variance and correlation time converging to common values independent of anesthesia. Compared to the case of no synaptic input, linearization of an approximating multivariate Ornstein-Uhlenbeck model reveals these effects to be the consequence of an additional slow eigenvalue associated with synaptic activity that competes with those of the underlying point neuron in a manner that depends on distance from spiking threshold.

Simultaneous extraction of propofol and propofol glucuronide from hair followed by validated LC–MS/MS analyses

Besides its clinical application, the anaesthetic agent propofol is being increasingly misused, mostly by healthcare professionals, and its abuse potential gained worldwide attention after the tragic death of Michael Jackson in 2009. Due to the short duration of its narcotic effects, propofol abuse is especially easy to hide compared with the use of other recreational drugs. However, propofol possesses a very narrow therapeutic window between the desired effect and potentially fatal toxicity, making abuse of the drug extremely dangerous even in experienced physicians. Consequently, it is important that forensic laboratories possess a sensitive and specific method for the detection of chronic propofol abuse. We present a simple, fast and reliable method to simultaneously extract propofol and its main metabolite propofol glucuronide from hair, followed by sensitive LC–MS/MS analyses, allowing to determine a chronic propofol abuse. Difficulties regarding the detection of propofol using LC–MS/MS were solved by using a derivatization reaction with 2-fluoro-1-methylpyridinium-p-toluene-sulfonate and triethylamine. Reliability of extraction method and subsequent LC–MS/MS analyses was confirmed under consideration of the validation parameters selectivity, linearity, accuracy and precision, analytical limits, processed sample stability, matrix effects and recovery. Appropriate quantification (LLOQ=10pg/mg hair) and detection limits (3.6pg/mg hair for propofol and 7.8 pg/mg hair for propofol glucuronide) could be achieved, enabling to detect even small amounts of both analytes. Applicability of the method was confirmed by analysis of three human hair samples from deceased with suspicion of chronic propofol abuse.

1,2-Dimethylimidazole-4-sulfonyl chloride (DMISC), a novel derivatization strategy for the analysis of propofol by LC-ESI-MS/MS.

Analysis of the anesthetic agent propofol in biological samples by LC-MS/MS is a great challenge due to weak fragmentation and poor ionization efficacy of propofol resulting in weak signal intensities. Improvements of the ionization and fragmentation efficacy can be achieved by conversion of propofol to its dimethylimidazolesulfonyl (DMIS) derivative by a derivatization reaction using 1,2-dimethylimidazole-4-sulfonyl chloride (DMISC). This DMIS derivative produced intense [M + H]+ ions in positive-ion LC-ESI-MS/MS with the dimethylimidazole moieties representing the most abundant product ions. Derivatization of serum samples is achieved by direct conversion of the acetonitrile supernatant of a protein precipitation with DMISC followed by a double liquid-liquid extraction using n-hexane. Reliability of the method was confirmed under consideration of the validation parameters selectivity, linearity, accuracy and precision, analytical limits, and processed sample stability. Linearity was demonstrated over the whole calibration range from 5 to 1000ng/ml with the use of a 1/x 2 weighting. Stability of the processed samples was verified for a time period of up to 25h. Due to its high sensitivity, appropriate quantification and detection limits (LLoQ = 5ng/ml, LoD = 0.95ng/ml) for toxicological propofol analyses could be achieved. Applicability of the method to biological samples could be verified by analysis of a human serum sample collected after propofol-induced sedation. Graphical abstract A novel derivatization strategy using 1,2-dimethylimidazole-4-sulfonyl chloride (DMISC) was developed to improve the ionization and fragmentation efficacy of propofol for LC-ESI-MS/MS analysis.

Synergistic Modulation of γ-Aminobutyric Acid Type A Receptor-Mediated Synaptic Inhibition in Cortical Networks by Allopregnanolone and Propofol

The neuroactive steroid allopregnanolone (ALLO) is an endogenous allosteric modulator of γ-aminobutyric acid type A (GABAA) receptors. There is evidence that ALLO, at physiologically relevant concentrations, modulates GABAA receptor function in the cerebral cortex. The widely used anesthetic agent propofol and ALLO share a similar mode of molecular action. Here, we ask how GABAA receptor-mediated synaptic inhibition and action potential firing of neurons in cultured cortical slices are altered by either ALLO or propofol or by coapplying both agents. We explored the effects of ALLO and propofol on spontaneous action potential activity of neocortical neurons in organotypic slices cultured from C57BL6 mice by performing extracellular multiunit recordings. Furthermore, we carried out whole-cell voltage-clamp experiments to quantify the drug effects on GABAA receptor-mediated tonic and phasic currents. We found that ALLO (100 nM) decreased multiunit action potential firing of neocortical neurons by approximately 21%. Moreover, the duration of GABAA receptor-mediated inhibitory postsynaptic currents (IPSCs) was prolonged (mean Δdecay time prolongation: 12.9 ± 2.2 milliseconds; n = 23), and a bicuculline-sensitive tonic current was induced (mean Δbaseline shift: -24.6 ± 13.6 pA; P = .002; n = 6). A subanesthetic concentration of propofol (250 nM) decreased the discharge rates of cortical neurons to a similar degree as ALLO (100 nM). ALLO and propofol administered in combination acted in an additive manner to reduce action potential firing. However, during ALLO administration, propofol was significantly more effective in enhancing GABAergic synaptic transmission. Propofol (250 nM) prolonged the inhibitory postsynaptic currents decay times by 10.4 ± 6.1 milliseconds (n = 9) with ALLO added to the bathing solution; in the absence of ALLO, however, propofol prolonged the decay time by only 3.8 ± 2 milliseconds (n = 13). In cortical neurons, GABAA receptor-mediated synaptic transmission is potentiated by ALLO and propofol in a synergistic manner, whereas the effects on spontaneous action potential activity appear additive. A coapplication of neurosteroids and propofol in general anesthesia and intensive care medicine may open new ways to reduce anesthetic dose requirements and, thus, avoid undesired anesthetic-induced side effects.

Effects of Anesthetic Agent Propofol on Postoperative Sex Hormone Levels.

Introduction: Several studies have found anesthetic agents including propofol in ovarian follicular fluid. However, little is known about the effect of anesthetic agents on ovarian function. We aimed to investigate whether there were differences in the postoperative levels of sex hormones when propofol was used as the anesthetic agent. Methods: A retrospective review was done of 80patients who underwent ovarian surgery, with 72 infertile women serving as controls. Patients were included in the study if their serum estradiol (E2) and follicle stimulating hormone (FSH) levels were measured during their first postoperative menstrual cycle. Results: Patients were grouped according to the use or non-use of propofol as follows: propofol group (n = 39) and non-propofol group (n = 41). The control group did not undergo surgery. Postoperative E2 levels did not differ between the three groups, but FSH levels were significantly higher in the patients who had undergone surgery compared to controls (p < 0.05). Post-hoc analysis of E2 and FSH levels in the propofol and non-propofol groups did not show any significant differences. Conclusions: The use of propofol did not result in any differences compared to other anesthetic agents in terms of postoperative sex hormone levels after gynecologic surgery. The type of anesthetic agent does not seem to affect the postoperative levels of female sex hormones.

How the cortico-thalamic feedback affects the EEG power spectrum over frontal and occipital regions during propofol-induced sedation.

Increasing concentrations of the anaesthetic agent propofol initially induces sedation before achieving full general anaesthesia. During this state of anaesthesia, the observed specific changes in electroencephalographic (EEG) rhythms comprise increased activity in the δ- (0.5-4 Hz) and α- (8-13 Hz) frequency bands over the frontal region, but increased δ- and decreased α-activity over the occipital region. It is known that the cortex, the thalamus, and the thalamo-cortical feedback loop contribute to some degree to the propofol-induced changes in the EEG power spectrum. However the precise role of each structure to the dynamics of the EEG is unknown. In this paper we apply a thalamo-cortical neuronal population model to reproduce the power spectrum changes in EEG during propofol-induced anaesthesia sedation. The model reproduces the power spectrum features observed experimentally both in frontal and occipital electrodes. Moreover, a detailed analysis of the model indicates the importance of multiple resting states in brain activity. The work suggests that the α-activity originates from the cortico-thalamic relay interaction, whereas the emergence of δ-activity results from the full cortico-reticular-relay-cortical feedback loop with a prominent enforced thalamic reticular-relay interaction. This model suggests an important role for synaptic GABAergic receptors at relay neurons and, more generally, for the thalamus in the generation of both the δ- and the α- EEG patterns that are seen during propofol anaesthesia sedation.

Comparative evaluation of propofol, sevoflurane and desflurane for neuroanaesthesia: A prospective randomised study in patients undergoing elective supratentorial craniotomy.

Background and Aims:Both inhalational and intravenous anaesthetic agents are being used for neuroanaesthesia. Clinical trials comparing “propofol and sevoflurane” and “desflurane and sevoflurane” have been published. However, the comparison of all the three anaesthetics in neurosurgical patients has not been done. A randomised clinical study was carried out comparing propofol, sevoflurane and desflurane to find the ideal neuroanaesthetic agent.Methods:A total of 75 adult patients undergoing elective craniotomy for supratentorial tumours were included in the study. The patients were induced with morphine 0.1 mg/kg and thiopentone 4-6 mg/kg. Neuromuscular blockade was facilitated with vecuronium. The patients were randomised to receive propofol, sevoflurane or desflurane along with nitrous oxide in oxygen for maintenance of anaesthesia. The neuromuscular blockade was reversed following the surgery once the patients opened eyes or responded to verbal commands. The three anaesthetics were compared for their effects on haemodynamics, brain relaxation and emergence characteristics.Results:The mean arterial blood pressure during anaesthesia was comparable among the groups. The patients receiving sevoflurane had faster heart rates intraoperatively when compared to desflurane (P < 0.05). The brain relaxation scores at various intraoperative time frames were comparable among the three groups (P > 0.05). The time to response to verbal commands were significantly prolonged with use of sevoflurane (8.0 ± 2.9 min) when compared to propofol (5.3 ± 2.9 min) and desflurane (5.2 ± 2.6 min) (P = 0.003). However, the time to emergence and the number of patients who had early emergence (<15 min) were comparable among the groups (P > 0.05). The quality of emergence (coughing and emergence agitation), as well as postoperative complications, were also comparable among the three groups.Conclusions:All the three anaesthetic agents-propofol, sevoflurane and desflurane appear comparable and acceptable with regard to their clinical profile during anaesthesia in patients undergoing elective supratentorial surgeries.

Anesthetic agent propofol inhibits myeloid differentiation factor 88-dependent and independent signaling and mitigates lipopolysaccharide-mediated reactive oxygen species production in human neutrophils in vitro

Engagement of toll-like receptor 4 (TLR4) can activate the myeloid differentiation factor 88 (MyD88)/toll-interleukin-1-resistance domain-containing adapter-inducing interferon-β (TRIF) dependent pathways, inducing production of reactive oxygen species (ROS) in neutrophils. Propofol (PPF) has both anti-oxidant and anti-inflammatory properties. However, the molecular mechanism by which PPF influences human neutrophil function is yet to be elucidated. This study aimed to investigate the influence of PPF on lipopolysaccharide (LPS)-induced reactive oxygen species production in human neutrophils. We isolated neutrophils from the peripheral blood of 10 healthy male donors. Neither 1µg/ml LPS nor 10–150μmol/L PPF influenced the rate of neutrophil apoptosis, but PPF significantly inhibited LPS-mediated reactive oxygen species production in a dose-dependent manner. PPF inhibited LPS-induced expression of MyD88, tumor necrosis factor receptor-associated factor 6, and TRIF, but not the expression of interferon regulatory factor 3 or phosphorylation of p47phox, p38-mitogen-activated protein kinase, and nuclear factor (NF)-κB, particularly in the neutrophils in which MyD88 or TRIF had been silenced by siRNA. The inhibitory effect of PPF on LPS-induced activation of p47phox, p38-mitogen-activated protein kinase, and NF-κB was partially antagonized by over-expression of MyD88 or TRIF in neutrophils. These observations provide insights into the mechanisms responsible for the anti-inflammatory properties of PPF. PPF reduces LPS-induced production of reactive oxygen species in neutrophils via inhibiting expression of MyD88 and TRIF signaling.

Inhibition of acid‐sensing ion channel currents by propofol in rat dorsal root ganglion neurons

Acid-sensing ion channels (ASICs), part of the epithelial sodium channel/degenerin family, are activated by extracellular protons. The ASICs play a significant role in the acidosis-mediated perception of pain. The anaesthetic agent propofol also exerts antinociceptive effects, but the underlying mechanisms for this effect are not clear. We used whole-cell patch clamping to investigate the effect of propofol on proton-gated currents in: (i) rat dorsal root ganglion (DRG) neurons; and (ii) HEK293 cells transfected with either ASIC1a or ASIC3. Propofol inhibited the amplitude of proton-gated currents in DRG neurons, but did not change the sensitivity of ASICs to H(+). Notably, propofol altered acid-evoked excitability of rat DRG neurons and decreased the number of action potentials induced by acid stimuli. In addition, we demonstrated that propofol inhibited ASICs by directly binding with these channels in HEK293 cells. These results suggest that propofol inhibits proton-gated currents in DRG neurons and that inhibition of proton-gated currents explains, in part, the antinociceptive effects of propofol in primary afferent neurons.

Valproic acid induced hyperammonaemic encephalopathy: case report

Hyperammonemia is a well-known adverse effect of valproic acid therapy. In the recent years, encephalopathy cases triggered by vaproic acid use-related hyperammonemia have been reported and regular blood ammonium level follow-up is suggested. Polypharmacy, malnutrition, urea cycle disorders are risk factors for encephalopathy triggered by vaproic acid related hyperammonemia. Here, we report a case of symptomatic non-hepatic encephalopathy during valproic acid treatment combined with electroconvulsive therapy (ECT). Valproic acid may have induced hyperammonemic encephalopathy in combination with the anesthetic agent propofol. We may suggest that patients receiving combination of valproic acid and propofol as induction agents for ECT, clinicians should be careful for the development of hyperammonaemic encephalopathy.