Effects Of Different Anesthetics Research Articles

Convergent effects of different anesthetics on changes in phase alignment of cortical oscillations.

Many anesthetics cause loss of responsiveness despite having diverse underlying molecular and circuit actions. To explore the convergent effects of these drugs, we examined how anesthetic doses of ketamine and dexmedetomidine affected oscillations in the prefrontal cortex of nonhuman primates. Both anesthetics caused increases in phase locking in the ventrolateral and dorsolateral prefrontal cortex, within and across hemispheres. However, the nature of the phase locking varied. Activity in different subregions within a hemisphere became more anti-phase with both drugs. Local analyses within a region suggested that this finding could be explained by broad cortical distance-based effects, such as large traveling waves. By contrast, homologous areas across hemispheres became more in-phase. Our results suggest that both anesthetics induce strong patterns of cortical phase alignment that are markedly different from those in the awake state, and that these patterns may be a common feature driving loss of responsiveness from different anesthetic drugs.

Experiencing anesthesia and surgery early in life impairs cognitive and behavioral development.

The impact of anesthesia and surgery on neurocognitive and behavioral development in infants and children remains inadequately understood. To investigate the impact of early-life exposure to general anesthesia and surgery on cognitive and behavioral development. Children aged 0-3 years who underwent general anesthesia and surgical procedures between 2012 and 2015 were included. The cognitive and behavioral development of these children at ages 4-6 years was assessed. Age-, race-, and gender-matched children from the same geographic region, who did not undergo general anesthesia or surgery, served as the control group. The Wechsler Preschool Primary Scale of Intelligence, Fourth Edition (WPPSI-IV) was used to evaluate children's total intelligence quotient (FSIQ) and specific cognitive domains. The Gesell Development Schedules (GSCH) and Child Behavior Checklist (CBCL) were employed to assess behavioral and personality development. Additionally, the study analyzed the effects of various factors including anesthesia drugs, surgery duration, number of surgeries, age, weight, ethnicity, and gender on postoperative neurocognitive and behavioral outcomes. The study included 447 children with anesthesia/surgical exposure (AS) and 459 children in the control group. Analysis of cognitive and behavioral development showed a significant difference in the working memory index (WMI) between the AS and control groups (p < 0.05). Exploratory findings indicated that children administered remifentanil exhibited lower developmental quotient (DQ) values, whereas those given fentanyl showed higher (worse) Child Behavior Checklist (CBCL) total scores. Moreover, increased anesthesia/surgical exposures, younger age and lower body weight at exposure, and longer surgery durations were associated with cognitive and behavioral developmental challenges. This study examined the impact of early-life exposure to surgery and anesthesia on postoperative cognitive and behavioral development. Findings indicate that higher frequency of exposure to surgery and anesthesia, younger age, and lower body weight at exposure could negatively influence cognitive and behavioral development. Furthermore, variations in the effects of different anesthetics on behavior and cognition were observed. Caution is advised regarding the use of opioid analgesics such as remifentanil and fentanyl for more rigorous clinical applications.

Impact of various anesthetic regimens on motor-evoked potentials in infants undergoing spinal surgery: A case series.

Motor-evoked potential (MEP) monitoring is commonly used in children. MEP monitoring in infants is difficult due to smaller signals requiring higher stimulation voltages. There is limited information on the effect of different anesthetics on MEP monitoring in this age group. This case series describes the effect of different anesthetic regimens on MEP monitoring in infants. Patients <1 year of age who underwent spinal surgery with MEP monitoring between February 2022 and July 2023 at a single tertiary care children hospital were reviewed. The motor-evoked potential amplitudes were classified into 4 levels based on the voltage in the upper and lower limbs (none, responded, acceptable, sufficient). "Acceptable" or "sufficient" levels were defined as successful monitoring. A total of 19 infants were identified, involving 3 anesthesia regimens: 4/19 (21.1%) cases were anesthetized with propofol/remifentanil total intravenous anesthesia (TIVA), 3/19 (15.8%) with propofol/remifentanil/low-dose sevoflurane and another 12/19 (63.2%) cases who initially received propofol/remifentanil/sevoflurane and were converted to propofol/remifentanil anesthesia intraoperatively. The 4 cases with propofol/remifentanil showed 20/32 (62.5%) successful monitoring points. In contrast, 6/24 (25%) successful points were achieved with propofol/remifentanil intravenous anesthesia/0.5 age-adjusted minimum alveolar concentration sevoflurane. In 12 cases converted from propofol/remifentanil/low-dose inhalational anesthetics to TIVA alone, successful MEP monitoring points increased from 46/96 (47.9%) to 81/96 (84.4%). Adding low-dose inhalation anesthetic to propofol-based TIVA suppresses MEP amplitudes in infants. The optimal anesthetic regimen for infants requires further investigation.

Attenuation of intestinal ischemia-reperfusion-injury by anesthetics: a potentially protective effect of anesthetic management in experimental studies.

Intestinal ischemia-reperfusion injury (IRI) is a potentially severe clinical syndrome after major surgical procedures. In addition to causing intestinal mucosa injury, intestinal IRI further damages distant organs, causing the severity of the condition in patients. So far, effective therapy for intestinal IRI is still absent, and the survival rate of the patients is low. Previous experimental studies have shown that some anesthetics can alleviate intestinal IRI and protect organs while exerting their pharmacological effects, indicating that reasonable perioperative anesthesia management may provide potential benefits for patients to avoid intestinal IRI. These meaningful findings drive scholars to investigate the mechanism of anesthetics in treating intestinal IRI in-depth to discuss the possible new clinical uses. In the present mini-review, we will introduce the protective effects of different anesthetics in intestinal IRI to help us enrich our knowledge in this area.

Effect of Different Anaesthetics on Hematology and Blood Biochemistry of Labeo rohita

The current study aims to determine the effect of four different anesthetics such as MS-222 (100 mg/L), tobacco extract (50 mg/L), propiscin (1.0 ml/L) and clove oil (40 mg/L) on the hematology and blood biochemical parameters of Labeo rohita. Blood was sampled 10 minutes after the anesthesia was administered and again after 24 hours. Except for the clove oil 24h measurements, there was a significant difference in the number of blood cells in all anesthetic applications (P&lt;0.05). Hemoglobin and hematocrit values were not altered after 24 hours of treatment with clove oil and propiscin. MCV, MCH and MCHC values were not significantly affected in any application except clove oil 24h. Biochemical parameters, including total protein and glucose level, significantly changed (P&lt;0.05) in propiscin and clove oil group. Enzymatic activities such as ALT changed significantly with MS-222, and AST values were nonsignificant (P&gt;0.05) with tobacco, Change has been detected in ALP with MS-222 and tobacco calcium and magnesium showed non-significant differences with anesthetics. Overall all the parameters were affected by anesthetics used in the current research, however, it was established that 24 hours following the administration of clove oil, the discrepancies in blood values had vanished to a great extent.

Retracted: Effects of Different Anesthetics on Perioperative Organ Protection and Postoperative Cognitive Function in Patients Undergoing Cardiac Valve Replacement with Cardiopulmonary Bypass.

[This retracts the article DOI: 10.1155/2022/8994946.].

Anesthetic‑specific lncRNA and mRNA profile changes in blood during colorectal cancer resection: A prospective, matched‑case pilot study.

Prometastatic and antitumor effects of different anesthetics have been previously analyzed in several studies with conflicting results. Thus, the underlying perioperative molecular mechanisms mediated by anesthetics potentially affecting tumor phenotype and metastasis remain unclear. It was hypothesized that anesthetic‑specific long non‑coding RNA (lncRNA) expression changes are induced in the blood circulation and play a crucial role in tumor outcome. In the present study, high‑throughput sequencing and quantitative PCR were performed in order to identify lncRNA and mRNA expression changes affected by two therapeutic regimes, total intravenous anesthesia (TIVA) and volatile anesthetic gas (VAG) in patients undergoing colorectal cancer (CRC) resection. Total blood RNA was isolated prior to and following resection and characterized using RNA sequencing. mRNA‑lncRNA interactions and their roles in cancer‑related signaling of differentially expressed lncRNAs were identified using bioinformatics analyses. The comparison of these two time points revealed 35 differentially expressed lncRNAs in the TIVA‑group, and 25 in the VAG‑group, whereas eight were shared by both groups. Two lncRNAs in the TIVA‑group, and 23 in the VAG‑group of insilico identified target‑mRNAs were confirmed as differentially regulated in the NGS dataset of the present study. Pathway analysis was performed and cancer relevant canonical pathways for TIVA were identified. Target‑mRNA analysis of VAG revealed a markedly worsened immunological response against cancer. In this proof‑of‑concept study, anesthesic‑specific expression changes in lncRNA and mRNA profiles in blood were successfully identified. Moreover, the data of the present study provide the first evidence that anesthesia‑induced lncRNA pattern changes may contribute further in the observed differences in CRC outcome following tumor resection.

Influence of Perioperative Anesthesia on Cancer Recurrence: from Basic Science to Clinical Practice.

In this review, we will summarize the effects of these perioperative anesthetics and anesthetic interventions on the immune system and tumorigenesis as well as address the related clinical evidence on cancer-related mortality and recurrence. Cancer remains a leading cause of morbidity and mortality worldwide. For many solid tumors, surgery is one of the major therapies. Unfortunately, surgery promotes angiogenesis, shedding of circulating cancer cells, and suppresses immunity. Hence, the perioperative period has a close relationship with cancer metastases or recurrence. In the perioperative period, patients require multiple anesthetic management including anesthetics, anesthetic techniques, and body temperature control. Preclinical and retrospective studies have found that these anesthetic agents and interventions have complex effects on cancer outcomes. Therefore, well-planned, prospective, randomized controlled trials are required to explore the effects of different anesthetics and techniques on long-term outcomes after cancer surgery. Due to the conflicting effects of anesthetic management on cancer recurrence, further preclinical and clinical trials are required and beneficial to the development of systemic cancer therapies.

USE OF BISPECTRAL INDEX (BIS) FOR MONITORING OF SEDATION AND TOTAL INTRAVENOUS ANESTHESIA (TIVA) IN PEDIATRIC PATIENTS UNDERGOING COLONOSCOPY

The objectives of this study were to determine whether there was a correlation between bispectral index (BIS) and Ramsey Sedation Scale (RSS) in regard to the type of sedation and total intravenous anesthesia (TIVA) during colonoscopy procedures in children, and to assess the utility of ketamine and propofol combination (ketofol) for this kind of procedures at children’s age. In our prospective study, 40 ASA I-II patients, 3 to 17 years of age, were randomly divided into two groups of 20 patients each. After premedication with atropine and midazolam, sedation was induced with propofol and fentanyl in Group PF, whereas in Group PK propofol and ketamine were used for induction. Both groups were further divided into two subgroups depending on whether anesthesia was maintained with intermittent doses or continuous infusion of propofol. Ketamine and/or fentanyl were administered as bolus doses. Heart rate (HR), peripheral oxygen saturation (SpO2), RSS and BIS values of all patients were recorded every 5 minutes throughout the colonoscopy procedures. The strongest degree of correlation between RSS and BIS existed when sedation or TIVA was maintained by the boluses of propofol and fentanyl. The use of ketamine significantly reduced the doses of propofol and fentanyl. BIS can be monitored in all pediatric patients in whom sedation and TIVA are administered during colonoscopy, but the effect of different anesthetics on the EEG signal should be considered in order to adequately assess the depth of sedation and anesthesia.Key words: awareness, monitoring, child, anesthetics, endoscopy

Effects of Different Anesthetics on Perioperative Organ Protection and Postoperative Cognitive Function in Patients Undergoing Cardiac Valve Replacement with Cardiopulmonary Bypass.

In this paper, we have carried out an experimental study to investigate the effects of different anesthetics on perioperative organ protection and postoperative cognitive function in patients undergoing cardiac valve replacement with cardiopulmonary bypass. To realize this idea, a total of 90 patients with single valve replacement under general anesthesia and hypothermic cardiopulmonary bypass from January 2020 to October 2021 were enrolled. These patients were assigned into three groups, with 30 cases in each group by the digital table method. Group A was anesthetized with sufentanil combined with dexmedetomidine. Group B was anesthetized with sufentanil combined with etomidate. Group C was anesthetized with sufentanil combined with propofol. Perioperative organ protection and postoperative cognitive function of the three groups were compared. At T0 time point, there was no significant difference in blood WBC, blood N, and CRP among groups A, B, and C (P > 0.05); At T4 and T5 time points, the indexes of blood WBC, blood N, and CRP in groups A, B, and C were higher compared to the T0 time point. At T4 and T5 time points, the indexes of blood WBC, blood N, and CRP in group A were significantly lower compared to group B and group C. Before treatment, there was no significant difference in ALT and AST among groups A, B, and C (P > 0.05). After treatment, the indexes of ALT and AST in group A were significantly lower compared to group B and group C at T4 and T5 time points (P < 0.05). Before treatment, there was no significant difference in urea and creatinine among groups A, B, and C (P > 0.05). After treatment, the urea and creatinine indexes of group A were significantly lower compared to group B and group C at T4 and T5 time points (P < 0.05). Before treatment, there was no significant difference in CK-MB and CTnl among groups A, B, and C (P > 0.05); After treatment, the indexes of CK-MB and CTnl in group A were significantly lower compared to group B and group C at T4 and T5 time points (P < 0.05). Before treatment, there was no significant difference in MOCA scores among groups A, B, and C (P > 0.05). After treatment, the MOCA scores of group A were significantly higher compared to group B and group C at T5 and T6 time points (P < 0.05). Sufentanil combined with dexmedetomidine for heart valve replacement under cardiopulmonary bypass can reduce the dosage of anesthetics during the operation and have a certain perioperative protective effect on important organs such as the heart, lung, liver, and kidney, which may be related to reducing intraoperative hemodynamic fluctuations and inhibiting inflammatory stress response.

The Effects of Sevoflurane vs. Propofol for Inflammatory Responses in Patients Undergoing Lung Resection: A Meta-Analysis of Randomized Controlled Trials.

Objective: Inflammatory cytokines are increased during one-lung ventilation in patients undergoing lung resection, and this increase can be fatal. Propofol and sevoflurane are the main anesthetics used for these patients. Unfortunately, there is no consensus on the best choice of an anesthetic agent concerning an inflammatory response in patients undergoing lung resection. This meta-analysis aimed to compare the effects of propofol and sevoflurane on the inflammatory response in patients undergoing lung resection.Methods: We searched electronic databases to identify randomized controlled trials comparing the effects of different anesthetics (sevoflurane vs. propofol) on the inflammatory response. The primary outcome concerned the concentration of systemic inflammatory cytokines. The secondary outcomes concerned the concentrations of inflammatory cytokines in the bronchoalveolar lavage (BAL) fluid from the dependent and independent lung. Random effects analysis of the meta-analyses were performed to synthesize the evidence and to assess the concentrations of inflammatory factors in the sevoflurane and propofol groups.Results: Eight trials involving 488 participants undergoing lung resection with one-lung ventilation were included. There was no significant difference in the concentrations of systemic interleukin (IL)-6, IL-10, or tumor necrosis factor α between the sevoflurane and propofol groups. Compared with the propofol group, BAL levels of IL-6 in the dependent ventilated lung were decreased in the sevoflurane group (three trials, 256 participants; standardized mean difference [SMD], −0.51; 95% confidence interval [CI], −0.90 to −0.11; p = 0.01; I2 = 46%). The BAL levels of IL-6 in the independent ventilated lung were also decreased by sevoflurane (four trials, 362 participants; SMD, −0.70; 95% [CI], −0.93 to −0.47; p < 0.00001; I2 = 0%).Conclusions: There was no difference in the systemic inflammatory response between the sevoflurane and propofol groups. However, compared with propofol, sevoflurane can reduce the local alveolar inflammatory response. Additional research is necessary to confirm whether the inflammatory response is direct or indirect.

Effect of general and local anesthesia on the vagal response characteristics during ganglionated plexus ablation

Abstract Funding Acknowledgements Type of funding sources: None. Background The effect of different anesthetics on the function of the autonomic nervous system (ANS) is not well known. As a relatively new treatment option, ganglionated plexus (GP) ablation aims to modify the behavior of the cardiac ANS to prevent some/all of the autonomic processes occurring in vasovagal syncope (VVS) by using endocardial ablation techniques. Purpose The purpose of this study was to determine the effects midazolam and propofol on the vagal response (VR) characteristics during GP ablation in patients with vasovagal syncope (VVS). Methods Forty consecutive patients undergoing GP ablation for VVS were divided to receive local anesthesia with midazolam (group 1, n = 29) or general anesthesia with propofol (group EA, n = 11). All GP sites were detected by using previously defined fragmented electrogram based strategy. VR was defined on 3 levels: 1) R-R interval increased by 50% (level 1); 2) R-R interval increased by 20-50% (level 2); and 3) R-R interval increase lower than 20% (level 3). Results Baseline characteristics and mean follow-up times were comparable between groups. In both groups, the left superior GP (LSGP) was the most common GP site at which a VR was observed. However, there was a significant difference between groups for level of VR. While ablation on the LSGP caused a level 1 VR in 89.6% of cases in group 1, level 1 VR was seen in 22.2% of cases in group 2 (p &amp;lt; 0.0001). Similarly, ratio of level 1 VR during ablation on the left inferior GP (LIGP) was significantly lower in group 2 (44.8% vs 9%, p = 0.034). Once cut-off for VR was decreased to level 2, the ratio of (+) VR increased to 90.9% during ablation on the LSGP in group 2. Level 2 VR was detected in 45.4% of cases during ablation on the LIGP. Ratio of positive VRs in any level was lower than 20% during ablation on the right superior and inferior GPs in both groups. During a mean follow-up time of 12.1 ± 7 months, all but 2 (5%) of 40 patients were free of syncope. Conclusions The autonomic nervous tone might be affected in different ways by local and general anesthesia. Propofol may reveal a shift in the sympathovagal balance toward sympathetic predominance which may cause a blunting on VR during GP ablation. Further randomized, controlled and multicenter studies should be performed to confirm these findings.

Understanding the Effects of Anesthesia on Cortical Electrophysiological Recordings: A Scoping Review.

General anesthesia in animal experiments is an ethical must and is required for all the procedures that are likely to cause more than slight or momentary pain. As anesthetics are known to deeply affect experimental findings, including electrophysiological recordings of brain activity, understanding their mechanism of action is of paramount importance. It is widely recognized that the depth and type of anesthesia introduce significant bias in electrophysiological measurements by affecting the shape of both spontaneous and evoked signals, e.g., modifying their latency and relative amplitude. Therefore, for a given experimental protocol, it is relevant to identify the appropriate anesthetic, to minimize the impact on neuronal circuits and related signals under investigation. This review focuses on the effect of different anesthetics on cortical electrical recordings, examining their molecular mechanisms of action, their influence on neuronal microcircuits and, consequently, their impact on cortical measurements.

Propofol and sevoflurane affect intra-operative memory formation of words differently: A prospective cohort study.

Memory priming seems possible even during apparently adequate anaesthesia. However, the effects of different anaesthetics and type of stimuli, by virtue of their specific neural underpinnings, have not been considered. To determine if intra-operative implicit memory is affected by the type of anaesthesia (propofol or sevoflurane) or by the type of stimuli (abstract or concrete words). Two consecutive, randomised controlled experiments. Neurological institute in Milan, Italy. Forty-three patients undergoing anaesthesia with propofol (experiment 1) and 32 patients undergoing anaesthesia with sevoflurane (experiment 2). Patients were ASA I or II, age 18 to 65 years, native Italian speakers, right-handed and without any condition affecting memory or hearing. During anaesthesia, the patients heard a list of either concrete or abstract words or no words at all (controls). Explicit memory was tested with an explicit recall task and the Brice Interview; implicit memory was assessed through a word stem completion test. The number of explicitly recalled words, positivity to the Brice Interview, the proportion of target and nontarget hits, and a derived implicit memory score. With propofol, the proportion of target hits was significantly greater than the proportion of nontarget hits for the concrete word experimental group (P = 0.018). The implicit memory score of the concrete word experimental group was significantly higher than the score of both the abstract word experimental group (P = 0.000) and the concrete word control group (P = 0.023). With sevoflurane, the proportion of target hits was significantly higher than the proportion of nontarget hits for the abstract word experimental group only (P = 0.027). No patients had a BIS above 60 and no one could recall intra-operative events or words. Intra-operative memory for words can form during apparently adequate BIS-guided anaesthesia but is modified by propofol or sevoflurane acting on different brain targets. Further studies on larger samples and using neuroimaging techniques are needed. Clinicaltrials.gov identifier: NCT03727464.

Differential Effect of Anesthesia on Visual Cortex Neurons with Diverse Population Coupling

Cortical neurons display diverse firing patterns and synchronization properties. How anesthesia alters the firing response of different neuron groups relevant for sensory information processing is unclear. Here we investigated the graded effect of anesthesia on spontaneous and visual flash-induced spike activity of different neuron groups classified based on their spike waveform, firing rate, and population coupling (the extent neurons conform to population spikes). Single-unit activity was measured from multichannel extracellular recordings in deep layers of primary visual cortex of freely moving rats in wakefulness and at three concentrations of desflurane. Anesthesia generally decreased firing rate and increased population coupling and burstiness of neurons. Population coupling and firing rate became more correlated and the pairwise correlation between neurons became more predictable by their population coupling in anesthesia. During wakefulness, visual stimulation increased firing rate; this effect was the largest and the most prolonged in neurons that exhibited high population coupling and high firing rate. During anesthesia, the early increase in firing rate (20–150 ms post-stimulus) of these neurons was suppressed, their spike timing was delayed and split into two peaks. The late response (200–400 ms post-stimulus) of all neurons was also suppressed. We conclude that anesthesia alters the visual response of primarily high-firing highly coupled neurons, which may interfere with visual sensory processing. The increased association of population coupling and firing rate during anesthesia suggests a decrease in sensory information content.

Effectiveness of anesthetic solutions for pain control in lower third molar extraction surgeries: a systematic review of randomized clinical trials with network meta-analysis.

To assess the effectiveness of different anesthetic solutions for pain control immediately after the extraction of lower third molars. Nine databases were used to identify randomized clinical trials, without restriction of language or year of publication. The "JBI Critical Appraisal Tools for Systematic Reviews" was used to assess the risk of bias in the studies. The network meta-analysis was performed to compare the effectiveness of different anesthetics to control the pain immediately after the surgery of lower third molars, using the standardized mean difference (SMD) as the effect estimate. The GRADE approach was used to assess the certainty of evidence. The search presented 13,739 initial results, from which 45 met the eligibility criteria and presented low to moderate risk of bias. Thirteen studies were included in the meta-analysis. The 2% lidocaine + clonidine presented the lowest pain scores (SMD = - 1.44; - 2.72 to - 0.16) compared to 4% articaine + adrenaline, followed by 0.5% bupivacaine + adrenaline (SMD = - 1.36; - 2.13 to - 0.59). The certainty of evidence varied between very low to moderate. 2% lidocaine + clonidine and 0.5% bupivacaine + adrenaline were the anesthetics with the highest probability for pain control immediately after the surgical procedure of removing impacted lower third molars. The use of an adequate anesthetic with effective pain control can contribute to a more comfortable postoperative period.

The effect of different anaesthetics on echocardiographic evaluation of diastolic dysfunction in a heart failure with preserved ejection fraction model

Heart failure with preserved ejection fraction (HFpEF) is currently untreated. Therapeutics development demands effective diagnosis of diastolic dysfunction in animal models mimicking human pathology, which requires appropriate anaesthetics. Here, we investigated which anaesthetic, ketamine/xylazine or isoflurane, could be used to reveal diastolic dysfunction in HFpEF-diseased obese ZSF1 rats by echocardiography. First, diastolic dysfunction was confirmed by pressure-volume loops in obese compared to lean control ZSF1 rats. In echocardiography, ketamine/xylazine, unlike isoflurane, was able to demonstrate impaired relaxation in obese ZSF1 rats, as reflected by impaired early (E) and late (A) filling peak velocities, decreased E/A ratio, and a prolonged deceleration and isovolumic relaxation time. Interestingly, ketamine/xylazine induced a wider separation of both tissue and pulsed wave Doppler-derived echocardiographic waves required for diastolic dysfunction diagnosis, potentially by reducing the heart rate (HR), while isoflurane resulted in merged waves. To assess whether HR-lowering alone explained the differences between the anaesthetics, echocardiography measurements under isoflurane with and without the HR-lowering drug ivabradine were compared. However, diastolic dysfunction could not be diagnosed in ivabradine-treated obese ZSF1 rats. In summary, ketamine/xylazine compared to isoflurane is the anaesthetic of choice to detect diastolic dysfunction by echocardiography in rodent HFpEF, which was only partly mediated by HR-lowering.

The Effects of Propofol and Sevoflurane on Postoperative Delirium in Older Patients: A Randomized Clinical Trial Study.

Postoperative delirium is associated with adverse postoperative outcomes. However, whether intravenous and inhalation anesthetics are associated with different risks of postoperative delirium remains unknown. We set up to determine the incidence and duration of postoperative delirium in older patients who had surgery under the intravenous anesthetic propofol or the inhalational anesthetic sevoflurane. Participants were patients who had total hip/knee replacements and were randomized to propofol (N = 106) or sevoflurane (N = 103) anesthesia group. The Confusion Assessment Method was employed by investigators who were blinded to the anesthesia regimen to assess the incidence and duration (days of postoperative delirium per person) of postoperative delirium on postoperative days 1, 2, and 3. A total of 209 participants (71.2±6.7 years old, 29.2% male) were included in the final data analysis. The incidence of postoperative delirium was 33.0% with propofol anesthesia and 23.3% with sevoflurane anesthesia (p = 0.119, Chi-square test), and we estimated that we would need 316 participants in each arm to detect a potential statistically significant difference. Days of postoperative delirium per person were higher in the propofol (0.5±0.8) anesthesia group compared to the sevoflurane anesthesia group (0.3±0.5, p = 0.049, Student's t-test). This pilot study established a system to compare effects of different anesthetics and generated a hypothesis that propofol trended to have a higher incidence and had longer duration of postoperative delirium than sevoflurane. Additional studies with a larger sample size are needed to test this hypothesis.

Differential effects of anaesthesia on the contractility of lymphatic vessels in vivo: authors’ reply

Differential effects of anaesthesia on the contractility of lymphatic vessels <i>in vivo</i>: authors’ reply

Volatile Anesthetic Sevoflurane Attenuates Toll-Like Receptor 1/2 Activation.

Although immunomodulatory effects of anesthetics have been increasingly recognized, their underlying molecular mechanisms are not completely understood. Toll-like receptors (TLRs) are one of the major receptors to recognize invading pathogens and danger signals from damaged host tissues to initiate immune responses. Among the TLR family, TLR2 and TLR4 recognize a wide range of ligands and are considered to be important players in perioperative pathophysiology. Based on our recent finding that volatile anesthetics modulate TLR4 function, we tested our hypothesis that they would also modulate TLR2 function. The effect of anesthetics isoflurane, sevoflurane, propofol, and dexmedetomidine on TLR2 activation was examined by reporter assays. An anesthetic that affected the activation was subjected to in silico rigid docking simulation on TLR2. To test our prediction that sevoflurane and a TLR1/TLR2 ligand Pam3CSK4 would compete for the same pocket of TLR2, we performed Pam3CSK4 competitive binding assay to TLR2 using HEK cells stably transfected with TLR2 (HEK-TLR2) with or without sevoflurane. We examined the effect of different anesthetics on the functions of human neutrophils stimulated with TLR2 ligands. Kruskal-Wallis test and Mann-Whitney U test were used for statistical analysis. We observed that the attenuation of TLR1/TLR2 activation was seen on sevoflurane exposure but not on isoflurane, propofol, or dexmedetomidine exposure. The attenuation of TLR2/TLR6 activation was not seen in any of the anesthetics tested. The rigid docking simulation predicted that sevoflurane and Pam3CSK4 bound to the same pocket of TLR1/TLR2 complex. The binding of Pam3CSK4 to HEK-TLR2 cells was impaired in the presence of sevoflurane, indicating that sevoflurane and Pam3CSK4 competed for the pocket, as predicted in silico. The stimulation of neutrophils with Pam3CSK4 induced L-selection shedding but did not affect phagocytosis and reactive oxygen species production. L-selectin shedding from neutrophils was attenuated only by sevoflurane, consistent with the result of our reporter assays. We found that TLR1/TLR2 activation was attenuated by sevoflurane, but we found no evidence for attenuation by isoflurane, propofol, or dexmedetomidine at clinically relevant concentrations. Our structural analysis and competition assay supported that sevoflurane directly bound to TLR2 at the interphase of the TLR1/TLR2 complex. Sevoflurane attenuated neutrophil L-selectin shedding, an important step for neutrophil migration.