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Abstract Delayed neurocognitive recovery after surgery is associated with increased morbidity and mortality. However, its mechanism of action remains controversial and complex. A prospective, double‐blind, randomized controlled trial was performed at the Affiliated Hospital of Zunyi Medical University. Older patients (aged 65 years and older) who underwent gastrointestinal surgery were randomly divided into sevoflurane‐based or propofol‐based anesthesia groups. The Mini‐Mental State Examination was performed to evaluate cognitive function. Peripheral venous blood was collected to test the levels of choline acetyltransferase and acetylcholinesterase. A total of 75 patients were enrolled and 30 patients in each group completed the study. On Day 1 postoperation, patients in the sevoflurane group showed worse performance on the Mini‐Mental State Examination than patients in the propofol group. Lower blood choline acetyltransferase concentrations and higher acetylcholinesterase concentrations were observed in patients who had sevoflurane anesthesia than in patients who had propofol anesthesia 1 day postoperative. At 3 days postoperation, patients with sevoflurane‐ or propofol‐based general anesthesia did not differ regardless of Mini‐Mental State Examination score or choline acetyltransferase and acetylcholinesterase levels. Sevoflurane‐based anesthesia has short‐term delayed neurocognitive recovery in older surgical patients, which may be related to central cholinergic system degeneration.

Although anesthesia provides favorable conditions for surgical procedures, recent studies have revealed that the brain remains active in processing noxious signals even during anesthesia. However, whether and how these responses affect the anesthesia effect remains unclear. The ventrolateral periaqueductal gray (vlPAG), a crucial hub for pain regulation, also plays an essential role in controlling general anesthesia. Hence, it was hypothesized that the vlPAG may be involved in the regulation of general anesthesia by noxious stimuli. Here, we found that acute noxious stimuli, including capsaicin-induced inflammatory pain, acetic acid-induced visceral pain, and incision-induced surgical pain, significantly delayed recovery from sevoflurane anesthesia in male mice, whereas this effect was absent in the spared nerve injury-induced chronic pain. Pretreatment with peripheral analgesics could prevent the delayed recovery induced by acute nociception. Furthermore, we found that acute noxious stimuli, induced by the injection of capsaicin under sevoflurane anesthesia, increased c-Fos expression and activity in the GABAergic neurons of the ventrolateral periaqueductal gray. Specific reactivation of capsaicin-activated vlPAGGABA neurons mimicked the effect of capsaicin and its chemogenetic inhibition prevented the delayed recovery from anesthesia induced by capsaicin. Finally, we revealed that the vlPAGGABA neurons regulated the recovery from anesthesia through the inhibition of ventral tegmental area dopaminergic neuronal activity, thus decreasing dopamine (DA) release and activation of DA D1-like receptors in the brain. These findings reveal a novel, cell- and circuit-based mechanism for regulating anesthesia recovery by nociception, and it is important to provide new insights for guiding the management of the anesthesia recovery period. [ABSTRACT FROM AUTHOR]

Our research aimed at investigating the protective effects in aged mice exposed to sevoflurane anesthesia. To assess learning and memory abilities and exploratory behavior, the novel object recognition (NOR) test, Morris water maze (MWM) test, and open field test were employed. Commercial kits were used to measure levels of malondialdehyde, nicotinamide adenine dinucleotide phosphate oxidase activity, superoxide dismutase activity, catalase activity, and iron. The messenger RNA and protein levels of ferritin heavy chain 1, nuclear factor erythroid 2-related factor 2 (Nrf2), heme oxygenase-1, and glutathione peroxidase 4 in the hippocampus were detected. Treatment with melatonin significantly ameliorated the decrease in exploration time of novel objects and the discrimination index induced by sevoflurane anesthesia. Melatonin also reduced escape latencies and increased the time spent in the target quadrant in the MWM test. In the open field test, melatonin-treated mice exhibited greater exploratory activity, including longer distances traveled and a higher number of rearing events. Further, melatonin treatment markedly decreased the levels of oxidative stress markers and iron in the hippocampus of aged mice exposed to sevoflurane anesthesia. However, the beneficial effects of melatonin were significantly attenuated following treatment with the Nrf2 inhibitor ML385. Our results suggest that melatonin could alleviate learning and memory impairment induced by sevoflurane anesthesia in aged mice through its antioxidant properties, partially through the Nrf2 pathway. [ABSTRACT FROM AUTHOR]

In this study, we aimed to validate the hypothesis that the interplay between sevoflurane, oxidative stress and ferroptosis is crucial for the pathogenesis of sevoflurane‐induced cognitive impairment in aged individuals. The mice with sevoflurane‐induced cognitive impairment were used to explore the effects of sevoflurane on oxidative stress, iron homeostasis, and cognitive function in aged mice. Iron content and oxidative stress markers were analyzed in hippocampal tissue homogenates using specific assays. Additionally, the levels of iron death‐related markers (Fth1 and Gpx4) were assessed by real‐time PCR and Western blotting. Morris Water Maze and novel object recognition (NOR) tests were conducted to evaluate cognitive function. Sevoflurane exposure in aged mice resulted in a significant increase in iron overloading in the hippocampus, followed by a subsequent stabilization. Oxidative stress levels were elevated in the hippocampal tissue of sevoflurane‐exposed mice, and a significant correlation was observed between iron death and oxidative stress. Liproxstatin‐1, a ferroptosis inhibitor, effectively ameliorated the decline in memory and learning abilities induced by sevoflurane anesthesia. Liproxstatin‐1 treatment reduced iron overload and oxidative stress in the hippocampal tissue of aged mice. The expression of Fth1 and Gpx4, iron death‐related markers, was downregulated following Liproxstatin‐1 intervention. Our findings suggest that sevoflurane anesthesia disrupts iron homeostasis, leading to increased oxidative stress and cognitive impairment in aged mice. These results highlight the potential of targeting iron‐mediated processes to mitigate sevoflurane‐induced cognitive impairment in the aging population. [ABSTRACT FROM AUTHOR]

Exposure to anesthesia in early life may cause severe damage to the brain and lead to cognitive impairment. The underlying mechanisms, which have only been investigated in a limited scale, remains largely elusive. We performed translatome and transcriptome sequencing together for the first time in hippocampus of neonatal mice that were exposed to sevoflurane. We treated a group of neonatal mice with 2.5 % sevoflurane for 2 h on day 6, 7, 8, 9 and treated another group on day 6, 7. We performed behavioral study after day 30 for both groups and the control to evaluate the cognitive impairment. On day 36, we collected translatome and transcriptome from the hippocampus in the two groups, compared the gene expression levels between the groups and the control, and validated the results with RT-qPCR. We identified 1750 differentially expressed genes (DEGs) from translatome comparison and 1109 DEGs from transcriptome comparison. As expected, translatome-based DEGs significantly overlapped with transcriptome-based DEGs, and functional enrichment analysis generated similar enriched cognition-related GO terms and KEGG pathways. However, for many genes like Hspa5, their alterations in translatome differed remarkably from those in transcriptome, and Western blot results were largely concordant with the former, suggesting that translational regulation plays a significant role in cellular response to sevoflurane. Our study revealed global alterations in translatome and transcriptome of mice hippocampus after neonatal exposure to sevoflurane anesthesia and highlighted the importance of translatome analysis in understanding the mechanisms responsible for anesthesia-induced cognitive impairment.

Huan He,1 Qichun Cui,1 Hengheng Chen,2,&ast; Xiao Huang,3,&ast; Shuai Wang,3,&ast; Tian Yu,2,&ast; Jinqiu Feng,3 Yun Shao1 1Department of Anesthesiology, Shanghai Stomatological Hospital & School of Stomatology, Fudan University, Shanghai, 200002, People’s Republic of China; 2Department of Preventive Dentistry, Shanghai Stomatological Hospital & School of Stomatology, Fudan University, Shanghai, 200002, People’s Republic of China; 3Department of Pediatric Dentistry, Shanghai Stomatological Hospital & School of Stomatology, Fudan University, Shanghai, 200002, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yun Shao, Department of Anesthesiology, Shanghai Stomatological Hospital & School of Stomatology, Fudan University, No. 356 East Beijing Road, Shanghai, 200002, People’s Republic of China, Tel/Fax +86 2163295852, Email shaoyun07078@sina.com Jinqiu Feng, Department of Pediatric Dentistry, Shanghai Stomatological Hospital & School of Stomatology, Fudan University, No 356 East Beijing Road, Shanghai, 200002, People’s Republic of China, Tel/Fax +86 2163601149, Email feng_jinqiu356@fudan.edu.cnPurpose: Sevoflurane is the preferred anesthetic agent for induction and maintenance of ambulatory surgery due to its property of fast onset and recovery. However, it has been recognized as one of the major contributors of emergence delirium. The aim of this study was to evaluate the preventive effect of intranasal dexmedetomidine on the occurrence of emergence delirium in pediatric patients under general anesthesia with sevoflurane.Patients and Methods: Ninety pediatric patients undergoing dental rehabilitation under sevoflurane anesthesia were enrolled in this study. The patients were divided into three groups (n=30 each in the 2 μg/kg dexmedetomidine, 1 μg/kg dexmedetomidine, and control with saline groups). The same volume (0.02mL/kg) of the mixed solution was dropped into the nasal cavity of the children 30 minutes before surgery. We used the Pediatric Anesthesia Emergence Delirium Scale (PAED) to assess the level and incidence of delirium in the post-anesthesia care unit.Results: Compared with the control group, prophylactic use of different dosages of intranasal dexmedetomidine significantly reduces the incidence of ED and severe ED in PACU (P< 0.001). Intranasal administration of 2 μg/kg dexmedetomidine was associated with a better acceptance of mask induction and a better tolerance of separation with parents.Conclusion: Both 2 μg/kg and 1 μg/kg intranasal dexmedetomidine can achieve ED preventive effects in PACU in dental rehabilitation under general anesthesia. A dosage of 2 μg/kg is more effective in preventing severe ED and providing better mask acceptance.Keywords: intranasal dexmedetomidine, emergence delirium, sevoflurane anesthesia, pediatric patients, dental rehabilitation

Introduction: The heterocyclic compound 4‐hydroxy‐(2,2,6,6‐Tetramethylpiperidin‐1‐yl)oxyl (TEMPOL) has a protective effect on neurological function in brain tissues damaged by ischemia and hypoxia. This study explored the effects of TEMPOL pretreatment on postoperative cognitive function in aged rats under sevoflurane anesthesia, focusing on inflammatory response and oxidative stress. Methods: Sixty male rats were divided into normal control (C), sevoflurane anesthesia (S), TEMPOL pretreatment (T), and sevoflurane anesthesia + TEMPOL pretreatment (ST) groups (15 per group). Groups T and ST rats received continuous intraperitoneal TEMPOL (100 mg/kg) for 3 days, while groups C and S rats were injected with 0.9% saline. After pretreatment, groups S and ST received 3% sevoflurane anesthesia. Results: Rats in group S exhibited a longer swimming distance, longer escape latency, lower frequency of platform crossing, and shorter dwell time in the targeted quadrant than those in groups C and T. Rats in group ST exhibited a shorter swimming distance, shorter escape latency, higher frequency of platform crossing, and longer dwell time in the targeted quadrant than those in group S. The expressions of interleukin‐6, tumor necrosis factor‐α, inducible nitric oxide synthase, and Ym1/2 messenger ribonucleic acid were higher in groups S and ST rats than in groups C and T rats and lower in group ST rats than in group S rat (p <.05). Superoxide dismutase (SOD), total antioxidant capacity (T‐AOC), and glutathione peroxidase (GSH‐Px) were lower, while malondialdehyde (MDA) was higher in groups S and ST rats than in groups C and T rats (p <.05). Group ST showed higher SOD, T‐AOC, and GSH‐Px, and lower MDA than group S (p <.05). Conclusions: TEMPOL pretreatment attenuated postoperative cognitive impairment induced by sevoflurane anesthesia in aged rats. This may be attributed to the downregulation of NR2B‐CREB‐BDNF pathway, reducing the inflammatory response and oxidative stress damage in hippocampal tissue. [ABSTRACT FROM AUTHOR]

Abstract Introduction The heterocyclic compound 4‐hydroxy‐(2,2,6,6‐Tetramethylpiperidin‐1‐yl)oxyl (TEMPOL) has a protective effect on neurological function in brain tissues damaged by ischemia and hypoxia. This study explored the effects of TEMPOL pretreatment on postoperative cognitive function in aged rats under sevoflurane anesthesia, focusing on inflammatory response and oxidative stress. Methods Sixty male rats were divided into normal control (C), sevoflurane anesthesia (S), TEMPOL pretreatment (T), and sevoflurane anesthesia + TEMPOL pretreatment (ST) groups (15 per group). Groups T and ST rats received continuous intraperitoneal TEMPOL (100 mg/kg) for 3 days, while groups C and S rats were injected with 0.9% saline. After pretreatment, groups S and ST received 3% sevoflurane anesthesia. Results Rats in group S exhibited a longer swimming distance, longer escape latency, lower frequency of platform crossing, and shorter dwell time in the targeted quadrant than those in groups C and T. Rats in group ST exhibited a shorter swimming distance, shorter escape latency, higher frequency of platform crossing, and longer dwell time in the targeted quadrant than those in group S. The expressions of interleukin‐6, tumor necrosis factor‐α, inducible nitric oxide synthase, and Ym1/2 messenger ribonucleic acid were higher in groups S and ST rats than in groups C and T rats and lower in group ST rats than in group S rat (p

Sevoflurane, commonly administered to children as anesthesia, often leads to emergence delirium (ED). Currently, a consensus is lacking among clinicians regarding pharmacological interventions to improve recovery. To determine an effective approach, we compared the effects of several drugs in lowering the incidence of ED after sevoflurane anesthesia in children. We searched online databases for relevant randomized controlled trials (59 studies selected; 5199 NMA-eligible participants) and performed a frequentist network meta-analysis (NMA). This study was registered on PROSPERO (number CRD: 42022329939). All included studies had a low to moderate risk of overall bias. The incidence of ED after sevoflurane anesthesia in children differed according to other drugs administered, and were ranked from high to low according to the surface under the cumulative ranking curve (SUCRA). Sufentanil (91.2%) and dexmedetomidine (77.6%) were more likely to reduce the incidence (SUCRA value) of ED, whereas the placebo (6.5%), ramelteon (11.1%), and magnesium (18%) were less likely to reduce the incidence of ED. Remifentanil (89.3%) ranked first in shortening emergence time, followed by placebo (82.4%) and ketamine (69.7%). Placebo shortened extubation time, followed by remifentanil (66.5%) and alfentanil (61.4%). Sufentanil and remifentanil lowered sevoflurane-induced ED incidences among children and shortened the emergence time more effectively than other drugs. Most adjuvant drugs that are combined with sevoflurane either do not change or may even prolong extubation time. Further research and clinical trials are required to support and update these conclusions. [ABSTRACT FROM AUTHOR]

Objective: In this study, we compared the efficacy of dexmedetomidine, clonidine, and placebo in the prevention of emergence delirium (ED) in children undergoing lower abdominal surgeries under sevoflurane anesthesia. Materials and Methods: We conducted a prospective randomized double-blinded study on 75 patients aged 4-10 years belonging to the American Society of Anesthesiologists I or II, undergoing lower abdominal surgeries of 1-2 h duration under sevoflurane anesthesia. The children were randomly distributed into three groups: dexmedetomidine (Group D), clonidine (Group C), and saline group (Group S). The study drug was administered 10 min after induction of anesthesia. Intraoperative hemodynamic parameters were recorded. The Pediatric Anesthesia Emergence Delirium (PAED) score was used to assess the incidence and severity of ED at 0, 5, 10, 15, 20, 30, 45, and 60 min of arrival to the postanesthesia care unit. A score of =10 was considered to have ED. The Ramsay Sedation Score and the Face, Legs, Activity, Cry, Consolability (FLACC) score were used to assess the degree of sedation and the severity of pain, respectively. Results: Dexmedetomidine showed the lowest incidence of ED while the highest incidence was seen in the saline group. The PAED score was lowest in the dexmedetomidine group, followed by clonidine, and highest in the control group at all time intervals. The Ramsay Sedation Score and FLACC score were also lower in the dexmedetomidine group as compared to the clonidine and saline groups. Conclusion: Dexmedetomidine was found to be more efficacious in preventing ED as compared to clonidine in children. [ABSTRACT FROM AUTHOR]

Objective: In this study, we compared the efficacy of dexmedetomidine, clonidine, and placebo in the prevention of emergence delirium (ED) in children undergoing lower abdominal surgeries under sevoflurane anesthesia. Materials and Methods: We conducted a prospective randomized double-blinded study on 75 patients aged 4–10 years belonging to the American Society of Anesthesiologists I or II, undergoing lower abdominal surgeries of 1–2 h duration under sevoflurane anesthesia. The children were randomly distributed into three groups: dexmedetomidine (Group D), clonidine (Group C), and saline group (Group S). The study drug was administered 10 min after induction of anesthesia. Intraoperative hemodynamic parameters were recorded. The Pediatric Anesthesia Emergence Delirium (PAED) score was used to assess the incidence and severity of ED at 0, 5, 10, 15, 20, 30, 45, and 60 min of arrival to the postanesthesia care unit. A score of ≥10 was considered to have ED. The Ramsay Sedation Score and the Face, Legs, Activity, Cry, Consolability (FLACC) score were used to assess the degree of sedation and the severity of pain, respectively. Results: Dexmedetomidine showed the lowest incidence of ED while the highest incidence was seen in the saline group. The PAED score was lowest in the dexmedetomidine group, followed by clonidine, and highest in the control group at all time intervals. The Ramsay Sedation Score and FLACC score were also lower in the dexmedetomidine group as compared to the clonidine and saline groups. Conclusion: Dexmedetomidine was found to be more efficacious in preventing ED as compared to clonidine in children.

BackgroundSevoflurane anesthesia is widely used in pediatric ambulatory surgery. However, emergency agitation (EA) and emergency delirium (ED), as major complications following sevoflurane anesthesia in children, pose risks to surgery and prognosis. Identifying the high risk of EA/ED, especially anesthesia exposure and the depth of anesthesia, may allow preemptive treatment.MethodsA total of 137 patients were prospectively enrolled in this single-center observational cohort study to assess the incidence of EA or ED. Multivariable logistic regression analyses were used to test the association between volatile anesthesia exposure and depth with EA or ED. The Richmond Agitation and Sedation Scale (RASS), Pediatric Anesthesia Emergence Delirium Scale (PAED) and Face, Legs, Activity, Cry, and Consolability (FLACC) behavioural pain scale was used to assess the severity of EA or ED severity and pain. Bispectral index (BIS) to monitor the depth of anesthesia, as well as TimeLOW−BIS/TimeANES %, EtSevo (%) and EtSevo-time AUC were included in the multivariate logistic regression model as independent variables to analyze their association with EA or ED.ResultsThe overall prevalence of EA and ED was 73/137 (53.3%) and 75/137 (54.7%) respectively, where 48/137 (35.0%), 19/137 (13.9%), and 6/137 (4.4%) had mild, moderate, and severe EA. When the recovery period was lengthened, the prevalence of ED and extent of FLACC decreased and finally normalized within 30 min in recovered period. Multivariable logistic regression demonstrated that intraoperative agitation [2.84 (1.08, 7.47) p = 0.034], peak FLACC [2.56 (1.70, 3.85) p 3,000, respectively. Peak FLACC [3.46 (2.13, 5.62) p

Remimazolam has been suggested to improve the maintenance of hemodynamic stability when compared with other agents used for general anesthesia. This study aimed to compare the effects of remimazolam and sevoflurane anesthesia on hemodynamic stability in patients undergoing robotic gastrectomy. We retrospectively reviewed the electronic medical records of 199 patients who underwent robotic gastrectomy with sevoflurane (n = 135) or remimazolam (n = 64) anesthesia from January to November 2021. Propensity scores were used for 1:1 matching between the groups. The primary outcome was the difference in use of intraoperative vasopressors between groups. Secondary outcomes included differences in incidence and dose of vasopressors, as well as intraoperative hemodynamic variables, between groups. Remimazolam anesthesia was associated with a significantly less frequent use of ephedrine (odds ratio (OR): 0.13; 95% confidence interval (CI): 0.05–0.38, p < 0.001), phenylephrine (OR: 0.12; 95% CI: 0.04–0.40, p < 0.001), and any vasopressor (OR: 0.06; 95% CI: 0.02–0.25, p < 0.001) compared with sevoflurane anesthesia. Remimazolam anesthesia enables better maintenance of hemodynamic stability than sevoflurane anesthesia. Thus, remimazolam anesthesia may be beneficial for patients who are expected to experience hypotension due to the combined effects of CO2 pneumoperitoneum and the head-up position utilized during robotic gastrectomy. [ABSTRACT FROM AUTHOR]

Background: Postoperative cognitive dysfunction (POCD) is one of the main causes of morbidity after noncardiac surgery; however, the pathogenic mechanisms of POCD have remained unclear until now. In this study, we performed a pilot study to investigate the association between apolipoprotein E (ApoE) ε4 and POCD in older patients undergoing intravenous anesthesia (IVA) and inhalation anesthesia (IAA). Methods: In total, 180 patients from Shenzhen People's Hospital were recruited and randomly divided into an IVA group and an IAA group. The IVA group and IAA group received propofol and sevoflurane treatment, respectively. Within 7 days after surgery, the mini-mental state examination (MMSE) was used daily to assess the cognitive function of both groups of patients. The genotypes of the ApoE gene were detected using the restriction fragment length polymorphism technique. In addition, the serum levels of (soluble protein-100β) S‑100β and (Interleukin- 6) L‑6 were also analyzed. Results: Compared to the preoperative and IVA groups, the MMSE score in the IAA group significantly decreased at 3 days after surgery. Furthermore, the IAA group had a higher percentage of patients who scored less than 25 points than the IVA group at 3 days after surgery. The decrease in the MMSE score was closely related to the ApoE ε4 allele in the IAA group, but this correlation was not observed in the IVA group. The levels of S‑100β and IL‑6 were increased sharply in patients with the ε4/ε4 genotype who received IAA compared with IVA at 1 day after surgery. Conclusion: The results of the study indicated that the ApoΕ ε4/ε4 genotype was a risk factor for early POCD in older patients undergoing sevoflurane anesthesia. [ABSTRACT FROM AUTHOR]

Background There are conflicting opinions on the effect of dexmedetomidine on cerebral autoregulation. This study assessed its effect on dynamic cerebral autoregulation (dCA) using a transcranial Doppler (TCD). Methods Thirty American Society of Anesthesiologists physical status I and II patients between 18 and 60 years, who underwent lumbar spine surgery, received infusions of dexmedetomidine (Group D) or normal saline (Group C), followed by anesthesia with propofol and fentanyl, and maintenance with oxygen, nitrous oxide and sevoflurane. After five minutes of normocapnic ventilation and stable bispectral index value (BIS) of 40–50, the right middle cerebral artery flow velocity (MCAFV) was recorded with TCD. The transient hyperemic response (THR) test was performed by compressing the right common carotid artery for 5–7 seconds. The lungs were hyperventilated to test carbon dioxide (CO2) reactivity. Hemodynamic parameters, arterial CO2 tension, pulse oximetry (SpO2), MCAFV and BIS were measured before and after hyperventilation. Dexmedetomidine infusion was discontinued ten minutes before skin-closure. Time to recovery and extubation, modified Aldrete score, and emergence agitation were recorded. Results Demographic parameters, durations of surgery and anesthesia, THR ratio (Group D: 1.26 ± 0.11 vs. Group C: 1.23 ± 0.04; P = 0.357), relative CO2 reactivity (Group D: 1.19 ± 0.34 %/mmHg vs. Group C: 1.23 ± 0.25 %/mmHg; P = 0.547), blood pressure, SpO2, BIS, MCAFV, time to recovery, time to extubation and modified Aldrete scores were comparable. Conclusions Dexmedetomidine administration does not impair dCA and CO2 reactivity in patients undergoing spine surgery under sevoflurane anesthesia.

Studies have shown that long-term exposure to sevoflurane (SEV) may cause postoperative cognitive dysfunction. This study aimed to investigate the effects of resveratrol (RES) treatment on the changes in the cognitive function of rats after prolonged anesthesia with SEV. Seventy-six adult male rats were used in this study. The SEV model was established under continuous anesthesia for 6 h. Rats were randomly classified into four groups as follows: control, SEV+vehicle, SEV+pre-RES (RES was administered 24 h before establishing the SEV model), and SEV+post-RES (RES was administered 1 h after establishing the SEV model) groups. Neurobehavioral outcomes and the potential mechanism underlying RES-mediated neuroprotection through the SIRT1/RhoA signaling pathway were evaluated. The water maze test showed that long-term exposure to SEV may lead to loss of learning and memory ability in rats (p0.05). Western blotting showed that SIRT1, RhoA, and cleaved Caspase-3 (CC3) expression significantly increased in the SEV+vehicle group (p

Although anesthesia provides favorable conditions for surgical procedures, recent studies have revealed that the brain remains active in processing noxious signals even during anesthesia. However, whether and how these responses affect the anesthesia effect remains unclear. The ventrolateral periaqueductal gray (vlPAG), a crucial hub for pain regulation, also plays an essential role in controlling general anesthesia. Hence, it was hypothesized that the vlPAG may be involved in the regulation of general anesthesia by noxious stimuli. Here, we found that acute noxious stimuli, including capsaicin-induced inflammatory pain, acetic acid-induced visceral pain, and incision-induced surgical pain, significantly delayed recovery from sevoflurane anesthesia in male mice, whereas this effect was absent in the spared nerve injury-induced chronic pain. Pretreatment with peripheral analgesics could prevent the delayed recovery induced by acute nociception. Furthermore, we found that acute noxious stimuli, induced by the injection of capsaicin under sevoflurane anesthesia, increased c-Fos expression and activity in the GABAergic neurons of the ventrolateral periaqueductal gray. Specific reactivation of capsaicin-activated vlPAG GABA neurons mimicked the effect of capsaicin and its chemogenetic inhibition prevented the delayed recovery from anesthesia induced by capsaicin. Finally, we revealed that the vlPAG GABA neurons regulated the recovery from anesthesia through the inhibition of ventral tegmental area dopaminergic neuronal activity, thus decreasing dopamine (DA) release and activation of DA D 1 -like receptors in the brain. These findings reveal a novel, cell- and circuit-based mechanism for regulating anesthesia recovery by nociception, and it is important to provide new insights for guiding the management of the anesthesia recovery period., Competing Interests: The authors declare no competing financial interests., (Copyright © 2024 the authors.)

Precise assessment of wakefulness states during sevoflurane anesthesia and timely arousal are of paramount importance to refine the control of anesthesia. To tackle this issue, a bidirectional implantable microelectrode array (MEA) is designed with the capability to detect electrophysiological signal and perform in situ deep brain stimulation (DBS) within the dorsomedial hypothalamus (DMH) of mice. The MEA, modified with platinum nanoparticles/IrOx nanocomposites, exhibits exceptional characteristics, featuring low impedance, minimal phase delay, substantial charge storage capacity, high double-layer capacitance, and longer in vivo lifetime, thereby enhancing the sensitivity of spike firing detection and electrical stimulation (ES) effectiveness. Using this MEA, sevoflurane-inhibited neurons and sevoflurane-excited neurons, together with changes in the oscillation characteristics of the local field potential within the DMH, are revealed as indicative markers of arousal states. During the arousal period, varying-frequency ESs are applied to the DMH, eliciting distinct arousal effects. Through in situ detection and stimulation, the disparity between these outcomes can be attributed to the influence of DBS on different neurons. These advancements may further our understanding of neural circuits and their potential applications in clinical contexts.

Purpose: Emergence delirium (ED) after sevoflurane anesthesia remains a serious issue in children. We aimed to compare different ratios of propofol-ketamine combinations to determine a better option for preventing ED., Design: A prospective, randomized clinical trial., Methods: In this study, 112 children aged between 3 and 12 years who underwent adenoidectomy and tonsillectomy were recruited. Propofol 1 mg kg -1 + ketamine 1 mg kg -1 (1:1 ratio), propofol 1.5 mg kg -1 + ketamine 0.75 mg kg -1 (2:1 ratio), propofol 2 mg kg -1 + ketamine 0.66 mg kg -1 (3:1 ratio), and propofol 3 mg kg -1 were applied at induction of anesthesia for Groups I, II, III, and IV, respectively. Fentanyl 1 mcg kg -1 and rocuronium 0.6 mg kg -1 were applied at induction, and anesthesia was maintained with sevoflurane and O 2 /N 2 O mixture for all participants. Intravenous morphine 0.1 mg kg -1 was applied for postoperative analgesia in the last 10 minutes of surgery. ED was defined as a Watcha score of ≥3. Demographics, hemodynamics, extubation time, Watcha scores, the Face, Legs, Activity, Cry, and Consolability scores, length of stay in the postanesthesia care unit (PACU), rescue analgesic requirement, and postoperative complications were recorded., Findings: ED was significantly higher at 10 and 20 minutes in Group IV. Eighteen children experienced ED in PACU, (3, 2, 2, and 11 children in Groups I, II, III, and IV, respectively). Face, Legs, Activity, Cry, and Consolability scores were significantly different at all times. Rescue analgesics were required by 3 children (10.7%) in Group I, 2 (7.1%) in Group II, 2 (7.1%) in Group III, and 10 (35.7%) in Group IV (P = .012). The PACU stay was 21.9 ± 6.4 in Group I, 18.7 ± 6.3 in Group II, 16.7 ± 5.8 in Group III, and 17.4 ± 5.8 in Group IV. Nystagmus was observed in three children in Group I., Conclusions: To addition of ketamine to propofol during the induction of sevoflurane anesthesia can reduce the ED and analgesic requirements in children. A propofol-to-ketamine ratio of 3:1 provided better postoperative recovery with less pain and ED, without prolonging the PACU length of stay., Competing Interests: Declaration of Competing Interest None., (Copyright © 2024 The American Society of PeriAnesthesia Nurses. Published by Elsevier Inc. All rights reserved.)

Sevoflurane is one of the most widely used anesthetics for the induction and maintenance of general anesthesia in surgical patients. Sevoflurane treatment may increase the incidence of postoperative cognitive dysfunction (POCD), and patients with POCD exhibit lower cognitive abilities than before the operation. POCD affects the lives of patients and places an additional burden on patients and their families. Understanding the mechanism of sevoflurane-induced POCD may improve prevention and treatment of POCD. In this paper, we review the diagnosis of POCD, introduce animal models of POCD in clinical research, analyze the possible mechanisms of sevoflurane-induced POCD, and summarize advances in treatment for this condition.

Sevoflurane is one of the most widely used anesthetics for the induction and maintenance of general anesthesia in surgical patients. Sevoflurane treatment may increase the incidence of postoperative cognitive dysfunction (POCD), and patients with POCD exhibit lower cognitive abilities than before the operation. POCD affects the lives of patients and places an additional burden on patients and their families. Understanding the mechanism of sevoflurane-induced POCD may improve prevention and treatment of POCD. In this paper, we review the diagnosis of POCD, introduce animal models of POCD in clinical research, analyze the possible mechanisms of sevoflurane-induced POCD, and summarize advances in treatment for this condition. [ABSTRACT FROM AUTHOR]

Mari Kawai,1 Shinji Kurata,1 Takuro Sanuki,2 Gaku Mishima,1 Kensuke Kiriishi,1 Toshihiro Watanabe,1 Yu Ozaki-Honda,1 Mizuki Yoshida,1 Ichiro Okayasu,1 Terumi Ayuse,3 Naomi Tanoue,3 Takao Ayuse1–31Department of Dental Anesthesia, Nagasaki University Hospital, Nagasaki, Japan; 2Nagasaki University Institute of Biomedical Sciences, Course of Medical and Dental Sciences, Dental Anesthesiology, Nagasaki, Japan; 3Department of Special Care Dentistry, Nagasaki University Hospital, Nagasaki, JapanBackground: Sevoflurane is generally the preferred anesthetic agent for general anesthesia in pediatric patients, due to its rapid induction and recovery characteristics. However, it has been recognized that a major complication is emergence agitation when awakening from general anesthesia. The aim of this study was to evaluate the occurrence rate of emergence agitation in the operating room and postoperative recovery area following intraoperative administration of midazolam to pediatric patients under general anesthesia.Patients and methods: One hundred and twenty pediatric patients undergoing dental treatment under sevoflurane anesthesia were enrolled in this study. The patients were divided into three groups (n=40 each in the 0.1 mg/kg midazolam, 0.05 mg/kg midazolam, and control with saline groups). Midazolam or saline was injected intravenously approximately 30 minutes before the end of the dental treatment. We used the Richmond Agitation and Sedation Scale (RASS) to assess the level of sedation and drowsiness at emergence phase in the operating room. We also used the Pediatric Anesthesia Emergence Delirium Scale (PAED) to assess the level of agitation and delirium at the full recovery phase from anesthesia in the recovery area.Results: At the emergence phase, the incidence of emergence agitation in the 0.1 mg/kg midazolam group was significantly lower than in the other groups (p=0.0010). At the recovery phase, there was no significant difference among the three groups. The odds ratio between PAED score and RASS score was 4.0 using logistic regression analysis. The odds ratio between PAED score and Disability was 2.5.Conclusion: Administration of a single dose of 0.1 mg/kg midazolam dose significantly decreases the incidence of severe emergence agitation at the emergence after sevoflurane anesthesia, but not at the recovery phase. Furthermore, the evaluation of sedative and agitation condition using RASS score at emergence from anesthesia is useful to predict occurrence of agitation in the recovery phase.Keywords: emergence agitation, sevoflurane anesthesia, pediatric patients, extreme non-cooperation against dental treatment

Exposure to anesthesia in early life may cause severe damage to the brain and lead to cognitive impairment. The underlying mechanisms, which have only been investigated in a limited scale, remains largely elusive. We performed translatome and transcriptome sequencing together for the first time in hippocampus of neonatal mice that were exposed to sevoflurane. We treated a group of neonatal mice with 2.5 % sevoflurane for 2 h on day 6, 7, 8, 9 and treated another group on day 6, 7. We performed behavioral study after day 30 for both groups and the control to evaluate the cognitive impairment. On day 36, we collected translatome and transcriptome from the hippocampus in the two groups, compared the gene expression levels between the groups and the control, and validated the results with RT-qPCR. We identified 1750 differentially expressed genes (DEGs) from translatome comparison and 1109 DEGs from transcriptome comparison. As expected, translatome-based DEGs significantly overlapped with transcriptome-based DEGs, and functional enrichment analysis generated similar enriched cognition-related GO terms and KEGG pathways. However, for many genes like Hspa5, their alterations in translatome differed remarkably from those in transcriptome, and Western blot results were largely concordant with the former, suggesting that translational regulation plays a significant role in cellular response to sevoflurane. Our study revealed global alterations in translatome and transcriptome of mice hippocampus after neonatal exposure to sevoflurane anesthesia and highlighted the importance of translatome analysis in understanding the mechanisms responsible for anesthesia-induced cognitive impairment., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 Published by Elsevier Ltd.)

The aim of us is to define the incidence of postoperative complications two anesthesia procedures. During the period between 01.01.2016 and 01.01.2017, totally 583 patients were included in the study, who had oral-maxillofacial surgeries. Anesthesia types were determined as propofol-based total intravenous anesthesia (TIVA) and sevoflurane-inhalation anesthesia (SA). Surgical types were divided into two groups, major and minor. Postoperative complications and recovery period were determined as tachycardia, bradycardia, hypertension, hypotension, recovery time, additional analgesia, nausea-vomiting. While TIVA was used 241 patients, SA was used 342 patients. Incidences of patients, having had major surgeries under TIVA, for additional analgesic, nausea-vomiting, and recovery period on average were found as 12.7%; 13.5%; 13min respectively. As for the patients having had minor surgeries under TIVA, the same values were 10.2%; 6.5%; 12min respectively. Incidences of patients, having had major surgeries under SA, for additional analgesic, nausea-vomiting, recovery period on average were found as 11.3%; 34.2%; 7min respectively. Patients having had minor surgeries under TIVA performed the same values as 9.8%; 19.5%; 5min respectively. It was observed that SA caused more nause-vomiting than TIVA; however, it had a shorter recovery period. We have been in the opinion of that SA absolutely must be done with nausea-vomiting premedication and that it could be preferred owing to the shorter recovery. [Med-Science 2018; 7(2.000): 290-4]

Background: There are conflicting opinions on the effect of dexmedetomidine on cerebral autoregulation. This study assessed its effect on dynamic cerebral autoregulation (dCA) using a transcranial Doppler (TCD). Methods: Thirty American Society of Anesthesiologists physical status I and II patients between 18 and 60 years, who underwent lumbar spine surgery, received infusions of dexmedetomidine (Group D) or normal saline (Group C), followed by anesthesia with propofol and fentanyl, and maintenance with oxygen, nitrous oxide and sevoflurane. After five minutes of normocapnic ventilation and stable bispectral index value (BIS) of 40-50, the right middle cerebral artery flow velocity (MCAFV) was recorded with TCD. The transient hyperemic response (THR) test was performed by compressing the right common carotid artery for 5-7 seconds. The lungs were hyperventilated to test carbon dioxide (CO2) reactivity. Hemodynamic parameters, arterial CO2 tension, pulse oximetry (SpO2), MCAFV and BIS were measured before and after hyperventilation. Dexmedetomidine infusion was discontinued ten minutes before skin-closure. Time to recovery and extubation, modified Aldrete score, and emergence agitation were recorded. Results: Demographic parameters, durations of surgery and anesthesia, THR ratio (Group D: 1.26 ± 0.11 vs. Group C: 1.23 ± 0.04; P = 0.357), relative CO2 reactivity (Group D: 1.19 ± 0.34%/mmHg vs. Group C: 1.23 ± 0.25%/mmHg; P = 0.547), blood pressure, SpO2, BIS, MCAFV, time to recovery, time to extubation and modified Aldrete scores were comparable. Conclusions: Dexmedetomidine administration does not impair dCA and CO2 reactivity in patients undergoing spine surgery under sevoflurane anesthesia. [ABSTRACT FROM AUTHOR]

The primary aim was to compare the changes in regional cerebral oxygen saturation (rSO 2) and cerebral blood flow velocity (CBFV) during sevoflurane and intravenous anesthesia when the end-tidal carbon dioxide partial pressure (P ET CO 2) changed in infants undergoing ventricular septal defect (VSD) repair. Prospective, observational study. Tertiary care hospital. Patients younger than 6 months with VSDs. End-tidal carbon dioxide was increased by decreasing tidal volume or respiratory rate. The infants were randomly assigned to receive either sevoflurane (SA group) or midazolam-sufentanil based intravenous anesthesia (IA group). P ET CO 2 levels of 30 mmHg (T1), 35 mmHg (T2), 40 mmHg (T3), or 45 mmHg (T4) were obtained by adjusting the tidal volume and respiratory rate. There were no significant intergroup differences in rSO 2. In the SA group, as P ET CO 2 increased from T1 to T4, rSO 2 increased significantly from 68.8% ± 5.9% to 76.4% ± 6.0% (p < 0.001). CBFV increased linearly, whereas the pulsatility index and resistance index decreased linearly from T1 to T4 (p < 0.001). In the IA group, rSO 2 showed a significant increase from 68.6% ± 4.6% to 76.1% ± 6.2% with the change in P ET CO 2 from T1 to T4 (p < 0.001). CBFV increased linearly, whereas the pulsatility index and resistance index decreased linearly from T1 to T4 (p < 0.001). Cerebrovascular response to different P ET CO 2 levels was preserved and similar during clinically relevant doses of sevoflurane anesthesia and midazolam-sufentanil based intravenous anesthesia in infants younger than 6 months old undergoing VSD repair. [ABSTRACT FROM AUTHOR]

Reactive oxygen species (ROS) are produced in excess when there is oxidative stress. Numerous pathological and physiological activities result in the production of ROS. Brain ischemia plays a crucial part in the pathophysiological process. One typical neurological complication following anesthetic surgery is postoperative cognitive impairment, which has grown to be a significant problem influencing older patients' postoperative recovery and quality of life. A popular clinical inhalation anesthetic, sevoflurane, has a stronger effect on postoperative cognitive performance in rats by inhibiting ROS, Ca2+ influx, and inflammation (Zhang et al. 2022; Liu et al. 2023). Numerous channels, including transient receptor potential (TRP) cation channels, voltage- and chemicalgated calcium channels, and others, increase Ca2+ influx. ROS triggers the activation of the TRP vanilloid 1 and TRP melastatin 7 subfamilies. When there is cerebral ischemia, anesthetic drugs are neuroprotective. In experimental models of ischemia, a variety of anesthetic protective mechanisms have been investigated, including the mitigation of TRP channel activation excitotoxicity through TRP channel blockage. Because anesthetics like isoflurane prevent intracellular Ca2+ influx in rats by blocking the TRP channel, which causes cognitive impairment, I will discuss the most recent research on the effects of sevoflurane anesthesia on TRP channels and oxidative stress in cerebral ischemia during my oral presentation. [ABSTRACT FROM AUTHOR]

OBJECTIVE: Exposure to volatile anesthetics in neonatal rats could induce neurotoxicity, learning deficits and abnormal social behaviors. The aim of this study is to investigate the potential neurotoxicity induced by sevoflurane. MATERIALS AND METHODS: Postnatal day 7 (P7) Sprague-Dawley (SD) rats were continuously exposed to 2% sevoflurane plus 40% oxygen/ air for 2 h. We used Morris water maze (MWM) to examine subsequent neurobehavioral performance. Transmission electron microscopy (TEM) was used to observe the histopathological changes in the hippocampus. RESULTS: Neonatal exposure to 2% sevo- flurane for 2 hours impaired short-term spatial working memory but not reference memory at P25. It induced synaptic ultrastructure impairments in the CA3 region of hippocampal, including fewer numbers of synapses, thinner thickness of postsynaptic dense, broader synaptic cleft width and smaller synaptic curvature. Our results also showed that all synaptic ultrastructure impairments and neurocognitive deficits had almost completely recovered at P53. CONCLUSIONS: We showed that a single sevoflurane exposure to neonatal rats led to temporary spatial working memory deficits. It might be associated with synaptic ultrastructure impairments in the CA3 region of the hippocampus, including fewer numbers of synapses, thinner thickness of PSD and broader synaptic cleft width. Fortunately, all the neurotoxicity and neurocognitive deficits were reversible. [ABSTRACT FROM AUTHOR]

The aim of the present study was to observe whether dexmedetomidine (DEX) combined with sufentanil decreased emergence agitation (EA) in children receiving sevoflurane anesthesia for cleft palate repair surgery. Children undergoing elective cleft palate repair surgery were randomly allocated into the DEX + sufentanil group (group DS; n=50) and the normal saline + fentanyl group (group SF; n=50). Patients in group DS were treated with 0.5 μg/kg DEX prior to induction of anesthesia, whereas patients in group SF received an equal volume of normal saline. Sufentanil (0.2 μg/kg) was administered to induce anesthesia, and 30 min before the end of surgery for patients in group DS. Fentanyl (2 μg/kg) was administered at the same time point for patients in group SF. Mean arterial pressure (MAP), heart rate (HR), duration of surgery and anesthesia, and the dosage of remifentanil were assessed. EA score, Pediatric Anesthesia Emergence Delirium (PAED) score and the Children and Infants Postoperative Pain Scale (CHIPPS) score were documented every 15 min in the post-anesthesia care unit (PACU). The number of cases requiring fentanyl (1 μg/kg) and the recovery profile data were analyzed. Compared with group DS (P<0.05) and the baseline (P<0.05), HR and MAP were significantly increased in group SF immediately following tracheal intubation and extubation. Mean values of maximum EA, PAED and CHIPPS scores were significantly reduced in group DS compared with group SF at 0 (P<0.01), 15 (P<0.05), and 30 min (P<0.05) after arrival at PACU. The incidence of EA in group SF was significantly increased compared with group DS (P<0.05). The dosage of remifentanil during the surgery and the number of cases requiring fentanyl (1 μg/kg) in group DS were significantly decreased compared with group SF (P<0.05). The findings of the present study suggested that DEX combined with sufentanil was able to effectively decrease the incidence of EA in children receiving sevoflurane anesthesia for cleft palate repair surgery. [ABSTRACT FROM AUTHOR]

BackgroundEmergence agitation (EA) in children after sevoflurane anesthesia is common. The purpose of this study was to compare the incidences of EA between ketamine and thiopental sodium induction in children underwent sevoflurane anesthesia. We also evaluated if a small dose of fentanyl could reduce the incidence of EA.MethodsThe patients who were scheduled for strabismus or entropion surgery were divided into 4 groups. The patients in Groups 1 and 2 were induced anesthesia with ketamine 1.5 mg/kg; those in Groups 3 and 4 were induced with thiopental sodium 5 mg/kg. The patients in Groups 1 and 3 received an injection of fentanyl 1.5 µg/kg, whereas the patients in Groups 2 and 4 received IV saline of the same volume. Anesthesia was maintained with sevoflurane. The recovery characteristics and EA in recovery room were assessed.ResultsThe incidence of EA was significantly higher in Groups 2 and 4 and there was no difference between Groups 2 and 4. Group 2 had almost an eleven-fold higher risk of developing EA than did Group 1, and the incidence of EA in Group 4 was sixty-nine-fold higher than that of Group 1. The risk factor for EA was only the kind of medication. Preoperative anxiety had no significant correlation with EA.ConclusionsThe incidence of EA after sevoflurane anesthesia is similar between ketamine and thiopental sodium anesthetic induction in children undergoing pediatric ophthalmic surgery. Also, the addition of a small dose of fentanyl after anesthetic induction decreases the incidence of EA.