Sevoflurane Anesthesia Research Articles

Remimazolam Reduces Vasopressor Use Post-Induction and During Maintenance of General Anesthesia in Patients Undergoing Laparoscopic Gynecology: A Propensity Score-Matched Analysis

Objectives: Laparoscopic gynecological surgeries are commonly performed under general anesthesia and can induce cardiovascular depression and hypotension, requiring vasopressor support. Remimazolam, a novel ultra-short-acting benzodiazepine, is used to treat minimal cardiovascular depression. This study compared the hemodynamic effects of remimazolam and sevoflurane anesthesia in patients undergoing laparoscopic gynecological surgery. Methods: A retrospective analysis was conducted on 474 patients who underwent laparoscopic gynecological surgery at Korea University Anam Hospital between September 2021 and December 2022. The patients were categorized into two groups based on the anesthetic agent used: remimazolam or sevoflurane. Hemodynamic parameters, vasopressor use, and intraoperative variables were compared between anesthetic agents. Propensity score matching was applied to account for potential confounders, and logistic regression was utilized to assess the relationship between anesthesia type and outcomes. Results: Remimazolam anesthesia was linked to a significantly lower incidence of vasopressor use compared to sevoflurane-based anesthesia (3.7% vs. 19.5%, p < 0.0001). The odds of requiring vasopressor support were significantly lower during the post-induction and maintenance phases in the remimazolam group. Furthermore, hemodynamic stability, particularly systolic and mean arterial pressures, was better maintained with remimazolam than sevoflurane. Conclusions: Remimazolam provides superior hemodynamic stability and reduces the need for vasopressor support during laparoscopic gynecological surgery compared with sevoflurane.

Comparative evaluation of hyaluronic acid-based dressing versus hydrocolloid dressing in rat dermal wound healing

Background: Wound healing is a complex process influenced by a variety of environmental factors. Dressing materials play a critical role in creating barriers against contaminants, maintaining optimal moisture levels, and absorbing wound exudate. Therefore, selecting materials tailored to wound characteristics is crucial for enhancing outcomes. Hyaluronic acid (HA) is a natural biocompatible polymer that supports healing by regulating inflammation and promoting tissue repair. This study compared HA- and hydrocolloid-based hydrogels in a rat model to optimize wound care strategies.Methods: Full-thickness dermal wounds (diameter, 8 mm) were created on the dorsal skin of 12 Sprague-Dawley rats under sevoflurane anesthesia. The wounds were treated with HA/silver sulfadiazine gel (group A), hydrocolloid gel (group B), or left untreated (control), all covered with a transparent dressing. Biopsy specimens on days 3, 7, and 21 were used to assess histological parameters: inflammatory cell infiltration, fibroblast infiltration, collagen deposition, neovascularization, and epithelial thickness, using a semi-quantitative scoring system. Histological analyses were conducted blindly, and statistical analyses were performed using the Kruskal-Wallis test (<i>p</i>< 0.05).Results: On day 3, group A showed significantly higher inflammatory cell infiltration and collagen deposition than other groups, indicating extracellular matrix formation. By day 7, angiogenesis was highest in group A, followed by group B and controls. By day 21, all wounds had completely healed. Epithelial layer thickness, reflecting inflammation and fibroblast maturity, was significantly higher in group A.Conclusion: This study compared HA-based hydrogel and hydrocolloid-based dressings through histological analyses to elucidate wound healing mechanics. HA-based hydrogel dressings significantly enhanced wound recovery. However, generalizing these outcomes requires future studies to expand the range of effective wound treatment materials. These findings underscore the potential of HA-based dressings to enhance clinical outcomes in wound management, suggesting avenues for improving therapeutic strategies.

Effects of vitamin E on calcium signaling and oxidative injury in neutrophils of patients with ischemia/reperfusion (surgical arthroscopy) under sevoflurane anesthesia

Sevoflurane is an anesthetic, and it acts on oxidative activity by activating Ca2+ influx. In human neutrophils, oxidative stress activates the voltage-gated calcium channels (VGCC) and the TRPM2 channel; on the other hand, these channels are inhibited by 2-aminoethoxydiphenyl borate (2-APB) and verapamil plus diltiazem (V+D), respectively. Under sevoflurane anesthesia, surgical arthroscopy poses a significant risk to oxidative stress and Ca2+ influx-induced neutrophil infiltration and injury of patients. However, vitamin E may inhibit lipid peroxidation (LP) by upregulating reduced glutathione (GSH) and glutathione peroxidase (GSH-Px) but downregulating TRPM2 and VGCC in the neutrophils of surgical arthroscopy patients. This topic was examined in the current study. We enrolled 20 patients in the current study, separating them into two primary groups: patients and patients plus vitamin E. Ten patients were divided into two groups: preoperative (N1) and postoperative (N2), both of which were not given vitamin E therapy. The remaining ten patients were given 300 IU of vitamin E two hours prior to their surgical arthroscopy (E1), and their blood was again drawn following the procedure (E2). Prior to fMLP stimulation, the isolated neutrophils from each of the four groups were cultured with 10 uM V+D and 100 uM 2-APB. In the neutrophils, there was an increase in intracellular free Ca2+ ([Ca2+]i) concentration and LP levels due to the downregulation of GSH and GSH-Px; however, following vitamin E treatment, GSH concertation and GSH-Px activity increased in the E2 group. While 2-APB and V+D treatment reduced the concentration of [Ca2+]i in the neutrophils, vitamin E administration had no effect on this measurement. In summary, vitamin E treatment mitigated the GSH and GSH-Px alterations induced by I/R damage, while TRPM2 and VGCC inhibition reduced the [Ca2+]i rise induced by I/R injury. One potential treatment approach for I/R-induced oxidative neutrophil damage is the suppression of TRPM2 and VGCC.

Assessment of the antinociceptive effect of a single fentanyl bolus dose in children: A pharmacokinetic and pharmacodynamic analysis based on the nociception level index during sevoflurane general anesthesia.

The Nociception Level Index has shown benefits in estimating the nociception/antinociception balance in adults, but there is limited evidence in the pediatric population. Evaluating the index performance in children might provide valuable insights to guide opioid administration. To evaluate the Nociception Level Index ability to identify a standardized nociceptive stimulus and the analgesic effect of a fentanyl bolus. Additionally, to characterize the pharmacokinetic/pharmacodynamic relationship of fentanyl with the Nociception Level Index response during sevoflurane anesthesia. Nineteen children, 5.3 (4.1-6.7) years, scheduled for lower abdominal or urological surgery, were studied. After sevoflurane anesthesia and caudal block, a tetanic stimulus (50 Hz, 60 mA, 5 s) was performed in the forearm. Following the administration of fentanyl 2 μg/kg intravenous bolus, three similar consecutive tetanic stimuli were performed at 5-, 15-, and 30-min post-fentanyl administration. Changes in the Nociception Level Index, heart rate, mean arterial pressure, and bispectral index were compared in response to the tetanic stimuli. Fentanyl plasma concentrations and the Nociception Level Index data were used to elaborate a pharmacokinetic/pharmacodynamic model using a sequential modeling approach in NONMEM®. After the first tetanic stimulus, both the Nociception Level Index and the heart rate increased compared to baseline (8 ± 7 vs. 19 ± 10; mean difference (CI95) -12(-18--6) and 100 ± 10 vs. 102 ± 10; -2(-4--0.1)) and decrease following fentanyl administration (19 ± 10 vs. 8 ± 8; 12 (5-18) and 102 ± 10 vs. 91 ± 11; 11 (7-16)). In subsequent tetanic stimuli, heart rate remained unchanged, while the Nociception Level Index progressively increased within 15 min to values similar to those before fentanyl. An allometric weight-scaled, 3-compartment model best characterized the pharmacokinetic profile of fentanyl. The pharmacokinetic/pharmacodynamic modeling analysis revealed hysteresis between fentanyl plasma concentrations and the Nociception Level Index response, characterized by plasma effect-site equilibration half-time of 1.69 (0.4-2.9) min. The estimated fentanyl C50 was 1.93 (0.73-4.2) ng/mL. The Nociception Level Index showed superior capability compared to traditional hemodynamic variables in discriminating different nociception-antinociception levels during varying fentanyl concentrations in children under sevoflurane anesthesia.

Research progress in the clinical application of inhaled anesthetic sevoflurane.

Sevoflurane has been widely used in clinical anesthesia as an inhalation anesthetic. With the development of medicine, there have been several new applications in recent years, such as daytime surgery, labor analgesia, and combined nerve block for some surgeries. Moreover, as research progresses, it has been found that it not only has potential organ protection effects but can also be used to treat severe asthma and relieve the tracheal spasm state. In addition, local administration can effectively treat vascular ulcers. We briefly review the organ protective effect of sevoflurane, its application in dental treatment, asthma treatment, vascular ulcer treatment and some new progress in clinical application.

Intranasal Dexmedetomidine-Esketamine Combination Premedication versus Monotherapy for Reducing Emergence Delirium and Postoperative Behavioral Changes in Pediatric Tonsillectomy and/or Adenoidectomy: A Randomized Controlled Trial.

Emergence delirium and postoperative negative behavioral changes (PNBC) are common complications in pediatric anesthesia. This study evaluated whether intranasal premedication combining dexmedetomidine and esketamine more effectively reduces these complications compared to either drug alone in children undergoing tonsillectomy and/or adenoidectomy with sevoflurane anesthesia. This randomized, double-blind trial involved 198 children aged 2-5 years undergoing tonsillectomy and/or adenoidectomy. Participants received intranasal premedication with either dexmedetomidine (2μg/kg), esketamine (1 mg/kg), or their combination (dexmedetomidine 1μg/kg plus esketamine 0.5 mg/kg). The primary outcome was the incidence of emergence delirium, defined as a Pediatric Anesthesia Emergence Delirium (PAED) scale score ≥ 10. Secondary outcomes included the incidence of PNBC, sedation depth, easiness of separation from parents, acceptance of the mask for induction, emergence time, postoperative pain score, parental satisfaction, and adverse events. The combination premedication significantly reduced emergence delirium incidence (9.4%) compared to esketamine alone (38.1%; relative risk [RR] 0.25, 95% confidence interval [CI] 0.11-0.57, p < 0.001), but not compared to dexmedetomidine alone (17.2%; RR 0.55, 95% CI 0.21-1.39, p = 0.193). PNBC incidence at day 7 was lower with the combination (28.1%) versus dexmedetomidine (48.4%; RR 0.58, 95% CI 0.36-0.93, p = 0.018), but not significantly different from esketamine alone (20.6%; RR 1.38, 95% CI 0.74-2.58, p = 0.326). The combination also provided significantly superior sedation, improved ease of separation from parents, better acceptance of the mask for induction, shorter emergence time, and higher parental satisfaction than both monotherapies. In children undergoing tonsillectomy and/or adenoidectomy with sevoflurane anesthesia, intranasal dexmedetomidine-esketamine premedication more effectively reduces emergence delirium compared to esketamine alone and PNBC compared to dexmedetomidine alone. This combination also improves sedation, shortens emergence times, and enhances parental satisfaction compared to monotherapy without significant adverse effects. The Chinese Clinical Trial Registry, ChiCTR2300076709.

Colchicine prevents perioperative myocardial injury in cardiac surgery by inhibiting the formation of neutrophil extracellular traps: evidence from rat models.

Colchicine, an anti-inflammatory agent, has been reported to improve myocardial infarction prognosis by inhibiting neutrophil extracellular traps (NETs) release. However, its role in cardiac surgery and the mechanisms behind NETs suppression remain unclear. This study aimed to explore colchicine's cardioprotective effects against perioperative myocardial injury in cardiac surgery, focusing on NETs inhibition as a novel therapeutic strategy. Male Sprague-Dawley rats were pre-treated with colchicine (0.1 mg/kg/day) or CI-amidine (10 mg/kg/day) for 7 days before undergoing cardiopulmonary bypass and myocardial ischaemia/reperfusion injury. The model was created by subjecting the rats to cardiopulmonary bypass and myocardial ischaemia/reperfusion injury. Under 4.0% sevoflurane anaesthesia, cardiopulmonary bypass was initiated by cannulating the tail artery and right atrium, and perfusion was maintained for 4 h. Immunofluorescence detected NETs, and haematoxylin and eosin staining assessed inflammatory cell. We found colchicine treatment significantly reduced perioperative myocardial injury in rats. Furthermore, we observed a notable elevation of NETs in the myocardial tissue of animal models. Moreover, suppressing peptidylarginine deiminase 4 was found to markedly diminish perioperative myocardial injury in rats. Additionally, colchicine can mitigate the release of NETs by inhibiting peptidylarginine deiminase 4. NETs were significantly elevated during the perioperative period of cardiac surgery. Colchicine significantly mitigated myocardial injury in cardiac surgery by inhibiting NETs formation, with peptidylarginine deiminase 4 inhibition being one of its mechanisms.

Effects of hydromorphone alone and combined with medetomidine-vatinoxan or dexmedetomidine on alfaxalone induction dose and mean arterial pressure in dogs anesthetized with sevoflurane

ObjectiveTo evaluate the dose of alfaxalone needed for induction of anesthesia following sedation with either medetomidine-vatinoxan plus hydromorphone (MVH), dexmedetomidine plus hydromorphone (DH), or hydromorphone (H) alone. A secondary objective included evaluating selected cardiopulmonary variables before, during, and after sedation and general anesthesia with sevoflurane in healthy dogs. Study designProspective, randomized, masked, crossover. AnimalsEight healthy Beagle dogs, 3–4 years old. MethodsAll dogs received three intramuscular (IM) treatments: H (0.1 mg kg-1), DH (0.005 mg kg -1 + 0.1 mg kg-1, respectively), or MVH (0.01 mg kg -1 + 0.2 mg kg -1 + 0.1 mg kg -1, respectively) at least 6 days apart. General anesthesia was induced with alfaxalone 20 minutes after treatment administration and maintained for 60 minutes with 2.8% sevoflurane (expired). Sedation scores, selected cardiopulmonary variables, and recovery scores were measured before, during, and after anesthesia at selected timepoints. Mixed effects ANOVA and ANOVA on ranks were used to evaluate differences between treatments, time, and their interaction, and Tukey-Kramer method was used for post-hoc analysis (p < 0.05). Data are presented as mean ± SD or median (range). ResultsDogs given MVH required a lower dose of alfaxalone for induction of anesthesia (0.77 ± 0.4 mg kg-1) compared to DH and H (1.16 ± 0.34 mg kg-1; p = 0.02, 1.13 ± 0.18 mg kg-1; p = 0.02), and had a higher incidence (50%; p = 0.038) and longer duration [median; 10 (0–35) minutes; ] of hypotension during sevoflurane anesthesia compared to H [0%; 0 (0–0) minutes; p = 0.040] but not DH (p = 0.272). Conclusions and clinical relevancePremedication with MVH provided the greatest alfaxalone-sparing effect. However, this treatment was associated with lower arterial pressures and clinically-relevant hypotension. Off-label use of medetomidine-vatinoxan before sevoflurane-based anesthesia should be used with caution due to a high incidence of hypotension.

Role of Hippocampal Glutamatergic Synaptic Alterations in Sevoflurane-Induced Cognitive Dysfunction in Aged Mice.

Perioperative neurocognitive disorders (PND), including postoperative delirium (POD) and postoperative cognitive dysfunction (POCD), are common following anesthesia and surgery in older patients and significantly increase morbidity and mortality. However, the underlying mechanism of PND is unclear. Our study aims to analyze the differentially expressed genes (DEGs) in excitatory neurons and investigate the role of hippocampal glutamatergic synaptic alterations in sevoflurane-induced cognitive dysfunction in aged mice. We performed single-nucleus RNA sequencing (snRNA-seq) technology to examine the alterations of excitatory neurons in hippocampus induced by sevoflurane in aged mice. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis of DEGs were performed in excitatory neurons. At last, immunofluorescence staining was used to validate sevoflurane-induced alternation of glutamatergic synapses in the hippocampus of aged mice. This study demonstrates that DEGs in excitatory neurons are associated with reduction of glutamatergic synapses and cognitive dysfunction. After immunofluorescence staining validation, we also confirmed that sevoflurane anesthesia decreased the density of glutamatergic synapses in the hippocampus of aged mice. Our findings demonstrated a key role of hippocampal glutamatergic synaptic alterations in sevoflurane-induced cognitive dysfunction in aged mice.

Trends in volatile anesthetic sevoflurane and desflurane usage and its impact on carbon emissions: A six-year audit at National Taiwan University Hospital (2018–2023)

This short communication presents an audit of anesthetic gas usage at National Taiwan University Hospital from 2018 to 2023. Using descriptive statistics and trend analysis, the data reveals trends in the consumption of sevoflurane and desflurane, associated costs, and their corresponding carbon emissions. A significant decrease in desflurane usage contributed to a 42.4% reduction in carbon dioxide equivalent (CO2e) emissions per general anesthesia case from 2018 to 2023. The findings underscore the importance of sustainable practices in anesthesia to align with global efforts to reduce carbon emissions.

Effects of prophylactic nalbuphine on emergence agitation and postoperative pain in pediatric patients undergoing ENT surgery with sevoflurane anesthesia.

Emergence agitation (EA) is a common complication in the pediatric population. This study aimed to investigate the effect of the prophylactic nalbuphine on EA in pediatric patients receiving sevoflurane anesthesia. The children undergoing ear, nose, and throat (ENT) surgery were administered 0.2 mg/kg nalbuphine (the nalbuphine group) or the same volume of normal saline (the control group) 5 min before the end of the surgery. The extubating time, time to eye-opening and duration of the post-anesthesia care unit (PACU) were recorded. Heart rate and blood pressure were monitored before and 5 min after nalbuphine administration. Pain was assessed using Face Legs Activity Cry and Consolability (FLACC) scales, and the drug-related postoperative complications (e.g., EA, delayed awakening, nausea and vomiting, and respiratory depression) were recorded. One-hundred and thirty pediatric patients were randomly divided into nalbuphine and control groups (n = 65). The nalbuphine group showed a significantly lower incidence of EA than the control group (20% vs. 46.2%, P = 0.002). No significant differences between the two groups were observed in heart rate and blood pressure 5 min after nalbuphine administration (P > 0.05). No significant differences were observed between the two groups regarding extubating time, time to eye-opening, and duration of PACU. The FLACC scales demonstrated lower values in the nalbuphine group than in the control group during the initial 4 h after the surgery. However, the FLACC scales showed similar values between 5 and 12 h after the surgery. In summary, the results of this study demonstrated that prophylactic natbuphine could minimize the incidence of EA in pediatric patients following ENT surgery without increasing the extubating time and PACU duration. http://www.chictr.org.cn, identifier [ChiCTR2300070046].

Short-term outcomes in infants following general anesthesia with low-dose sevoflurane/dexmedetomidine/remifentanil versus standard dose sevoflurane (The TREX trial).

The TREX (Trial Remifentanil DEXmedetomidine) trial aimed to determine if, in children < 2 years old, low-dose sevoflurane/dexmedetomidine/remifentanil anesthesia (LD-SEVO) is superior to standard dose sevoflurane (STD-SEVO) anesthesia in terms of global cognitive function at 3 years of age. The aim of the present secondary analyses was to compare incidence of intraoperative hypotension and bradycardia, postoperative pain, time to recovery, need for treatment of intraoperative hypotension and bradycardia, incidence of light anesthesia and need for treatment, need for postoperative pain medications, and morbidity and mortality outcomes at 5 days between the two arms. This Phase III randomized active controlled, parallel group, assessor blinded, multicenter, superiority trial was performed in 20 centers in Australia, Italy, and the United States. Four hundred and fifty-five infants <2 years of age expected to undergo general anesthesia for at least 2 hours were enrolled. They were randomized between LD-SEVO and STD-SEVO. The short-term perioperative outcomes noted above were compared between these two groups. There was less hypotension (risk difference -11.6%, 95% confidence interval (CI) -18.9% to -4.3%) and more bradycardia (risk difference 18.2%, 95% CI 8.8% to 27.7%) in the LD-SEVO compared to the STD-SEVO arm. There were more patients with episodes of light anesthesia (89 vs. 4), and protocol abandonments (1 vs. 0) in the LD-SEVO arm. Time from eye-opening to Post Anesthesia Care Unit (PACU) discharge was similar in both arms, as were morbidity and mortality. One patient in each arm suffered a life-threatening event but neither suffered long-term sequelae. These early postoperative results suggest that in children less than 2 years of age receiving greater than 2 hours of general anesthesia, the low-dose sevoflurane/dexmedetomidine/remifentanil anesthesia technique and the standard sevoflurane anesthesia technique are broadly clinically similar, with no clear evidence to support choosing one technique over the other.

Sevoflurane anesthesia during late gestation induces cognitive disorder in rat offspring via the TLR4/BDNF/TrkB/CREB pathway.

Sevoflurane (Sevo) is widely used for general anesthesia during pregnancy. Emerging evidence indicates that maternal Sevo exposure can trigger developmental neurotoxicity in the offspring. Nonetheless, the underlying mechanisms need further investigation. Pregnant Sprague-Dawley rats on gestational day 18 were exposed to 3.5% Sevo to induce the rat model of neurotoxicity. TAK-242, a TLR4 inhibitor, was administrated to inhibit the signaling transduction. Hippocampal tissues of rat offspring were harvested for immunohistochemical staining, TUNEL staining, Western blotting, ELISA, and measurement of oxidative stress-related markers. Serum samples were collected to evaluate lipid metabolism-associated factors. Morris water maze was implemented to test the cognitive function of offspring rats. Rat hippocampal neurons were isolated to elucidate the effect of TAK-242 on the BDNF/TrkB/CREB signaling in vitro. The results showed that maternal Sevo exposure during the third trimester induced neuroinflammation, lipid metabolism disturbance, and oxidative stress, and impaired the spatial learning and memory of rat offspring. Sevo upregulated TLR4 and impeded BDNF/TrkB/CREB signaling transduction in the hippocampus of rat offspring; TAK-242 administration reversed these effects. In conclusion, Sevo anesthesia during late gestation impairs the learning and memory ability of rat offspring possibly by promoting neuroinflammation and disturbing lipid metabolism via the TLR4/BDNF/TrkB/CREB pathway.

GDNF facilitates cognitive function recovery following neonatal surgical-induced learning and memory impairment via activation of the RET pathway and modulation of downstream effectors PKMζ and Kalirin in rats

ObjectiveThe aim of this study is to elucidate the underlying mechanism through which glial cell line-derived neurotrophic factor (GDNF) improves cognitive deficits in adults resulting from neonatal surgical interventions. MethodsNewborn Sprague–Dawley rats, regardless of gender, were randomly allocated into seven groups on postnatal day 7 as follows (n=15): (1) Control group (not subjected to anesthesia, surgery, or any pharmaceutical interventions); (2) GDNF group (received intracerebroventricular injection of GDNF); (3) Surgery group (underwent right carotid artery exposure under anesthesia with 3 % sevoflurane); (4) Surgery plus GDNF group; (5) Surgery plus GDNF and type II JAK inhibitor NVP-BBT594 (BBT594) group (administered intraperitoneal injection of BBT594); (6) BBT group; and (7) Surgery plus BBT group. Starting from postnatal day 33, all rats underwent Barnes maze and fear conditioning tests, followed by decapitation under sevoflurane anesthesia for subsequent analyses. The left hemibrains underwent Golgi staining, while the right hemibrains were used for hippocampal protein extraction to assess Protein kinase Mζ (PKMζ) and Kalirin expression through western blotting. ResultsGDNF demonstrated a mitigating effect on spatial learning and memory impairment, as well as context-related fear memory impairment, reductions in dendritic total lengths, and spinal density within the hippocampus induced by surgical intervention. Notably, all of these ameliorative effects of GDNF were reversed upon administration of the RET inhibitor BBT594. Additionally, GDNF alleviated the downregulation of protein expression of PKMζ and Kalirin in the hippocampus of rats subjected to surgery, subsequently reversed by BBT594. ConclusionThe effective impact of GDNF on learning and memory impairment caused by surgical intervention appears to be mediated through the RET pathway. Moreover, GDNF may exert its influence by upregulating the expression of PKMζ and Kalirin, consequently enhancing the development of dendrites and dendritic spines.

Sevoflurane in the Acute Phase of Severe Traumatic Brain Injury

The aim of the study was to evaluate the usefulness and safety of sevoflurane in patients in the acute phase of severe traumatic brain injury (TBI).Materials and methods. A prospective, randomized, pilot clinical trial was conducted at the Sklifosovsky Research Institute for Emergency Medicine (Moscow) in adults with acute severe TBI, aged 18 years and older, undergoing intensive intracranial pressure (ICP)-guided therapy. To achieve the desired sedative effect, the inhaled anesthetic sevoflurane was administered in the main group, and standard doses of intravenous propofol were administered in the control group. ICP and cerebral oxygen extraction fraction (OEF) were monitored in all patients. Hemodynamic and respiratory support parameters, transcranial Doppler ultrasound scan, brain bioelectrical activity, brain CT scan, laboratory parameters, markers of inflammation, patients' need for sedation and mechanical ventilation, and length of ICU stay were also evaluated.Results. The use of inhalation sedation contributed to the reduction of ICP on day 2 (9.5 mmHg in the sevoflurane group and 17.3 mmHg in the propofol group, P=0.003) and day 3 (10 mmHg and 14.2 mmHg, respectively, P=0.005). BIS monitoring showed no significant difference in depth of sedation between groups on day 2 (60 vs. 48.5, P=0.070) and day 3 (61 vs. 46, P=0.095). Inhalation sedation reduced cerebral OEF on the injury side compared to propofol on day 2 (23.3 vs. 30.2%, P=0.006) and day 3 (22.7 vs. 31.2%, P&lt;0.001). After 24 hours of sedation therapy, there was a significant difference in P/F (PaO₂/FiO₂) ratios between the groups. On days 1, 3, and 7, the sevoflurane group had P/F ratios of 340, 324, and 323 mmHg, while the propofol group had significantly lower ratios of 271, 278, and 275 mmHg (P&lt;0.001). Pneumonia was documented in 9 cases in the sevoflurane group vs. 18 cases in the propofol group (P=0.028), and a similar trend was observed in the total number of infectious complications: 13 vs. 21 cases, respectively (P=0.046).Conclusion. Sevoflurane in the acute phase of severe TBI was not only safe, but also improved several vital functions, including ICP, blood pressure, P/F ratio, and also slowed brain metabolism via reduced oxygen consumption without affecting the depth of sedation according to BIS monitoring data. All of the above suggests that inhalation sedation may improve the prognosis for patient recovery. However, multicenter randomized clinical trials are needed to identify and verify all positive and negative effects of inhalation sedation in this patient population.

A hypothalamus-lateral periaqueductal gray GABAergic neural projection facilitates arousal following sevoflurane anesthesia in mice.

The lateral hypothalamus (LHA) is an evolutionarily conserved structure that regulates basic functions of an organism, particularly wakefulness. To clarify the function of LHAGABA neurons and their projections on regulating general anesthesia is crucial for understanding the excitatory and inhibitory effects of anesthetics on the brain. The aim of the present study is to investigate whether LHAGABA neurons play either an inhibitory or a facilitatory role in sevoflurane-induced anesthetic arousal regulation. We used fiber photometry and immunofluorescence staining to monitor changes in neuronal activity during sevoflurane anesthesia. Opto-/chemogenetic modulations were employed to study the effect of neurocircuit modulations during the anesthesia. Anterograde tracing was used to identify a GABAergic projection from the LHA to a periaqueductal gray (PAG) subregion. c-Fos staining showed that LHAGABA activity was inhibited by induction of sevoflurane anesthesia. Anterograde tracing revealed that LHAGABA neurons project to multiple arousal-associated brain areas, with the lateral periaqueductal gray (LPAG) being one of the dense projection areas. Optogenetic experiments showed that activation of LHAGABA neurons and their downstream target LPAG reduced the burst suppression ratio (BSR) during continuous sevoflurane anesthesia. Chemogenetic experiments showed that activation of LHAGABA and its projection to LPAG neurons prolonged the anesthetic induction time and promoted wakefulness. In summary, we show that an inhibitory projection from LHAGABA to LPAGGABA neurons promotes arousal from sevoflurane-induced loss of consciousness, suggesting a complex control of wakefulness through intimate interactions between long-range connections.

Effect of Sevoflurane Anesthesia on Diastolic Function: A Prospective Observational Study.

The effect of sevoflurane on left ventricular diastolic function is not well understood. We hypothesized that parameters of diastolic function may improve under sevoflurane anesthesia in patients with preexisting diastolic dysfunction compared to patients with normal diastolic function. This observational study included 60 patients undergoing breast surgery or laparoscopic cholecystectomy. Patients were assigned to diastolic dysfunction (n = 34) or normal (n = 26) groups of septal e' < 8 or ≥ 8.0 cm/s on the first thoracic echocardiography (TTE) performed before anesthesia. During anesthesia, sevoflurane was maintained at 1 to 2 minimum alveolar concentration (MAC) to maintain the bispectral index at 40 to 50. At the end of surgery, the second TTE was performed under 0.8 to 1 MAC of sevoflurane with the patient breathing spontaneously without ventilator support. Primary end point was the percentage change (Δ) of e' on 2 TTEs (Δe'). Secondary end points were ΔE/e', Δleft atrial volume index (ΔLAVI), and Δtricuspid regurgitation maximum velocity (ΔTR Vmax). These percentage changes (Δ) were compared between diastolic dysfunction and normal groups. e' (Δe': 30 [6, 64] vs 0 [-18, 11]%; P < .001), mitral inflow E wave velocity (E), mitral inflow E/A ratio (E/A), and mitral E velocity deceleration time (DT) improved significantly in diastolic dysfunction group compared to normal group. LAVI decreased in diastolic dysfunction group but did not reach statistical significance between the 2 groups (ΔLAVI:-15 [-31, -3] vs -4 [-20, 10]%, P = .091). ΔE/e' was not different between the 2 groups (11 [-16, 26] vs 12 [-9, 22]%, P = .853) (all: median [interquartile range, IQR]). TR was minimal in both groups. In this study, echocardiographic parameters of diastolic function, including septal e', E, E/A, and DT, improved with sevoflurane anesthesia in patients with preexisting diastolic dysfunction, but remained unchanged in patients with normal diastolic function.

Berberine Alleviates Sevoflurane Anesthesia-Induced Cognitive Dysfunction in Neonatal Mice via Regulating CREB1.

Sevoflurane has been shown to stimulate neurotoxicity and lead to cognitive impairment. Berberine is known for its role in regulating nervous system diseases, including cognitive dysfunction. This study aimed to investigate the effects of berberine on cognitive dysfunction induced by sevoflurane anesthesia and its potential mechanisms. In the in vivo study, neonatal mice were subjected to sevoflurane anesthesia to induce cognitive dysfunction. The cognitive function of the neonatal mice was evaluated using the Morris water maze test, open field test, and tail suspension test. Enzyme-linked immunosorbent assay (ELISA) was utilized to assess the levels of inflammatory factors. Immunohistochemistry (IHC) was conducted to detect ionized calcium-binding adaptor molecule 1 (IBA-1)-positive cells and cleaved caspase-3-positive cells in the hippocampus of the neonatal mice. Western blotting was used to measure the levels of cyclic adenosine monophosphate (cAMP) response element-binding protein 1 (CREB1) in hippocampal tissues and neurons. Hippocampal neurons were isolated from the hippocampus of neonatal mice. These neurons were treated with berberine or subjected to cell transfection. The cell counting kit-8 (CCK-8) assay and terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL) assay were conducted to measure cell viability and apoptosis of hippocampal neurons in vitro. Berberine significantly attenuated sevoflurane-induced cognitive impairment and inflammation in neonatal mice (p < 0.05 or p < 0.01). Additionally, berberine reduced sevoflurane-triggered neuronal apoptosis in the hippocampus of neonatal mice (p < 0.01). Sevoflurane markedly decreased CREB1 expression in the hippocampus of neonatal mice (p < 0.01), which was elevated by berberine treatment (p < 0.01). Mechanistically, sevoflurane significantly suppressed cell viability and promoted cell apoptosis of hippocampal neurons (p < 0.0001 or p < 0.01), which were mitigated by berberine (p < 0.05, p < 0.01, or p < 0.001). Furthermore, berberine significantly elevated CREB1 expression in sevoflurane-treated hippocampal neurons (p < 0.01). The beneficial effects of berberine on cell viability and apoptosis in sevoflurane-treated hippocampal neurons were blocked by CREB1 depletion (p < 0.001). Our results demonstrated that CREB1 was significantly decreased in the hippocampus of sevoflurane-treated neonatal mice in vivo and in sevoflurane-treated hippocampal neurons in vitro. This decrease was mitigated by berberine treatment. Moreover, berberine improved sevoflurane anesthesia-induced cognitive impairment in neonatal mice by attenuating neuronal inflammation and apoptosis in vivo. The inhibitory effects of berberine on sevoflurane-induced cell apoptosis were reversed by CREB1 downregulation. These findings indicate that berberine protects against sevoflurane anesthesia-induced cognitive impairment by reducing apoptosis of hippocampal neurons, partially through increasing CREB1 expression.

Emergence Delirium in children

Delirium after anesthesia, also known as emergence delirium (ED) is a clinical condition in which patients have alterations to their attention, awareness, and perceptions. In children, this often results in behavioral disturbances such as crying, sobbing, thrashing and disorientation. Emergence Agitation (EA) and Emergence Delirium (ED) are commonly used interchangeably; they describe two distinct conditions with emergence delirium being described in the anesthesia literature as a state of mental confusion, agitation, and dis-inhibition marked by some degree of hyper-excitability during recovery from general anesthesia. The commonly reported incidence of emergence delirium is about 10% to 30% of paediatric patients. Risk factors associated with emergence delirium are age, preexisting behaviours, types of surgery and the use of volatile anaesthesia. Transient agitation - delirium from sevoflurane anesthesia can lead to a variety of adverse events, such as airway spasm, shedding or displaced tracheal tube, dehiscence, or bleeding. Volatile anaesthetics may affect brain activity by interfering with the balance between neuronal synaptic inhibition and excitation in the central nervous system. Elevated postoperative pain has been suggested to underlie ED. But given that ED is seen in patients undergoing MRI, pain cannot be the sole cause. Treatment options include the use of premedication, analgesic adjuvants, single dose of propofol at the conclusion of the case. Midazolam premedication, intraoperative dexmedetomidine and fentanyl were associated with lower incidence of ED. The incidence of ED in patients receiving propofol is markedly lower than those receiving sevoflurane, despite the similar rapid emergence profile of both agents. Paediatric Assessment of Emergence Delirium (PAED) scale, developed specifically for children, is a valid and reliable scale. Watcha score is a simpler, reliable tool to measure emergence behaviour. There has been considerable progress in the neuroscience of anaesthesia and the application of new pharmacological agents, but the mystery behind the exact mechanism of ED is elusive. ED is a diagnosis of exclusion once other causes have been dismiss. There is no strong evidence of long-term effects and outcomes in children who developed emergence delirium after anesthesia. Prevention may be the best treatment but no one medication is entirely effective.

Evaluation of the Effect of Different Inhalation Agents on Ovaries with Hyperthermic Intraperitoneal Chemotherapy: An Experimental Study.

Background and Objectives: Cisplatin is a chemotherapeutic drug that is frequently used with hyperthermic intraperitoneal chemotherapy (HIPEC). Cisplatin-induced gonadotoxicity leads to a depletion of the ovarian reserve, causing premature ovarian insufficiency. This study aimed to investigate the impact of hyperthermia on cisplatin-induced ovarian toxicity and to determine whether sevoflurane or desflurane could be a more appropriate choice of anesthetic for reducing ovarian toxicity in HIPEC procedures. Materials and Methods: A total of 24 New Zealand rabbits were randomly divided into 4 groups as follows: Group H: HIPEC (cisplatin 7 mg/kg), Group HS: HIPEC (cisplatin 7 mg/kg) + 3% sevoflurane (2 h), Group HD: HIPEC (cisplatin 7 mg/kg) + 6% desflurane (2 h), and Group C: Control (Saline). Two catheters were placed in the abdominal cavity, the upper and lower quadrants. The perfusate was heated to 42 °C and given intraperitoneally for 90 min at a rate of 4 mL/min by catheters. Ovarian tissues were collected for Hematoxylin and Eosin staining and immunohistochemical analysis. Results: The primary follicle number was significantly decreased in Group H and HD compared to the C group (p < 0.05). Bax expression was high in Group H, according to all groups (p < 0.0001). Bax expression significantly decreased after sevoflurane, compared to group H (p = 0.012). The bcl-2 expression decreased in all groups compared to the C group. Bcl-2 expression was increased with sevoflurane compared to the H group (p = 0.001). Caspase 3 and p53 expression increased in all groups compared to the C group. p53 expression was decreased with sevoflurane and desflurane compared to the H group (p = 0.002, p = 0.008, respectively). Conclusions: The application of cisplatin with the intraoperative HIPEC method caused ovarian damage. According to our results, sevoflurane anesthesia could be a better option in mitigating cell death I the n ovarian reserve (follicle count) and apoptosis in the HIPEC procedures. We think that our findings should be supported by large series of clinical and experimental studies.