Sevoflurane Anesthesia Research Articles

Sodium Leak Channel in Glutamatergic Neurons of the Lateral Parabrachial Nucleus Helps to Maintain Respiratory Frequency Under Sevoflurane Anesthesia.

The lateral parabrachial nucleus (PBL) is implicated in the regulation of respiratory activity. Sodium leak channel (NALCN) mutations disrupt the respiratory rhythm and influence anesthetic sensitivity in both rodents and humans. Here, we investigated whether the NALCN in PBL glutamatergic neurons maintains respiratory function under general anesthesia. Our results showed that chemogenetic activation of PBL glutamatergic neurons increased the respiratory frequency (RF) in mice; whereas chemogenetic inhibition suppressed RF. NALCN knockdown in PBL glutamatergic neurons but not GABAergic neurons significantly reduced RF under physiological conditions and caused more respiratory suppression under sevoflurane anesthesia. NALCN knockdown in PBL glutamatergic neurons did not further exacerbate the respiratory suppression induced by propofol or morphine. Under sevoflurane anesthesia, painful stimuli rapidly increased the RF, which was not affected by NALCN knockdown in PBL glutamatergic neurons. This study suggested that the NALCN is a key ion channel in PBL glutamatergic neurons that maintains respiratory frequency under volatile anesthetic sevoflurane but not intravenous anesthetic propofol.

Postoperative liver injury after sevoflurane or propofol anesthesia in patients undergoing non-cardiac surgery: a retrospective cohort study

Although sevoflurane is generally considered safe, reports suggest that sevoflurane may cause postoperative liver injury more frequently than previously believed. Therefore, we aimed to compare the incidence of clinically significant postoperative liver injury following non-cardiac surgery between patients who underwent sevoflurane anesthesia and propofol-based total intravenous anesthesia. We retrospectively reviewed adult surgical patients from January 2010 to September 2022 who underwent general anesthesia in our center using sevoflurane or propofol over 3 h. After 1:1 propensity score matching, the incidence of postoperative liver injury was compared between the two groups. Out of 58,300 patients reviewed, 44,345 patients were included in the analysis. After propensity score matching, 7767 patients were included in each group. The incidence of postoperative liver injury was 1.4% in the sevoflurane group, which was similar to that in the propofol group (1.6%; p = 0.432). Comparison of the severity of postoperative alanine aminotransferase elevation showed that the incidence of borderline and mild elevation was higher in the sevoflurane group, but there was no difference in the incidence of moderate and severe elevation. In conclusion, sevoflurane anesthesia over 3 h was not associated with a higher incidence of clinically significant postoperative liver injury compared to propofol anesthesia.

Dysregulation of the Gut Microbiota Contributes to Sevoflurane-Induced Cognitive Dysfunction in Aged Mice by Activating the NLRP3 Inflammasome.

Postoperative cognitive dysfunction (POCD), a common complication in elderly patients after surgery, seriously affects patients' quality of life. Long-term or repeated inhalation of sevoflurane can cause neuroinflammation, which is a risk factor for POCD. However, the underlying mechanism needs to be further explored. Recent research had revealed a correlation between neurological disorders and changes in the gut microbiota. Dysfunction of the gut microbiota is involved in the occurrence and development of central nervous system diseases. Here, we found that cognitive dysfunction in aged mice induced by sevoflurane exposure (3%, 2 hours daily, for 3 days) was related to gut microbiota dysbiosis, while probiotics improved cognitive function by alleviating dysbiosis. Sevoflurane caused a significant decrease in the abundance of Akkermansia (P<0.05), while probiotics restored the abundance of Akkermansia. Compared to those in the control group, sevoflurane significantly increased the expression of NLRP3 inflammasome-associated proteins in the gut and brain in the sevoflurane-exposed group, thus causing neuroinflammation and synaptic damage, which probiotics can mitigate (con vs. sev, P < 0.01; p+sev vs. sev, P < 0.05). In conclusion, for the first time, our study revealed that dysbiosis of the gut microbiota caused by sevoflurane anesthesia contributes to the NLRP3 inflammasome-mediated neuroinflammation and cognitive dysfunction from the perspective of the gut-brain axis. Perhaps postoperative cognitive impairment in elderly patients can be alleviated or even prevented by regulating the gut microbiota. This study provides new insights and methods for the prevention and treatment of cognitive impairment induced by sevoflurane.

Astrocytic GDNF ameliorates anesthesia and surgery-induced cognitive impairment by promoting hippocampal synaptic plasticity in aged mice

BackgroundPerioperative neurocognitive disorders (PND) are common complications after surgery in older patients. However, the specific mechanism of this condition remains unclear. Glial cell line-derived neurotrophic factor (GDNF) is an important neurotrophin that abundantly expressed throughout the brain. It can enhance synaptic plasticity and alleviate learning and memory impairments. Thus, the purpose of this study was to investigate the role of GDNF in PND and the mechanisms involved. MethodsThe PND animal model was established by performing left tibial fracture surgery on 18-month-old C57BL/6 mice under sevoflurane anesthesia. Recombinant adeno-associated virus (rAAV)-GDNF or empty vectors were injected bilaterally into the hippocampal CA1 region of aged mice 3 weeks before anesthesia/surgery. The open field and fear conditioning test were used to assess the behavior changes. Golgi staining and electrophysiology were utilized to evaluate the morphological and functional alterations of neuronal synaptic plasticity. Western blot analysis was carried out to measure the proteins expression levels and immunofluorescence staining was performed to probe the cellular localization of GDNF. ResultsMice with surgery and anesthesia showed a significant decrease in hippocampus-dependent learning and memory, accompanied by a decline in hippocampal synaptic plasticity. Anesthesia/surgery induced a reduction of GDNF, which was colocalized with astrocytes. Overexpression of GDNF in astrocytes could ameliorate the decline in cognitive function by improving hippocampal synaptic plasticity, meanwhile astrocytic GDNF rescued the anesthesia/surgery-induced decrease in GFRα1 and NCAM. ConclusionThe study concludes that astrocytic GDNF may improve anesthesia/surgery-induced cognitive impairment by promoting hippocampal synaptic plasticity in aged mice via the GFRα1/NCAM pathway.

Substance specific EEG patterns in mice undergoing slow anesthesia induction

The exact mechanisms and the neural circuits involved in anesthesia induced unconsciousness are still not fully understood. To elucidate them valid animal models are necessary. Since the most commonly used species in neuroscience are mice, we established a murine model for commonly used anesthetics/sedatives and evaluated the epidural electroencephalographic (EEG) patterns during slow anesthesia induction and emergence. Forty-four mice underwent surgery in which we inserted a central venous catheter and implanted nine intracranial electrodes above the prefrontal, motor, sensory, and visual cortex. After at least one week of recovery, mice were anesthetized either by inhalational sevoflurane or intravenous propofol, ketamine, or dexmedetomidine. We evaluated the loss and return of righting reflex (LORR/RORR) and recorded the electrocorticogram. For spectral analysis we focused on the prefrontal and visual cortex. In addition to analyzing the power spectral density at specific time points we evaluated the changes in the spectral power distribution longitudinally. The median time to LORR after start anesthesia ranged from 1080 [1st quartile: 960; 3rd quartile: 1080]s under sevoflurane anesthesia to 1541 [1455; 1890]s with ketamine. Around LORR sevoflurane as well as propofol induced a decrease in the theta/alpha band and an increase in the beta/gamma band. Dexmedetomidine infusion resulted in a shift towards lower frequencies with an increase in the delta range. Ketamine induced stronger activity in the higher frequencies. Our results showed substance-specific changes in EEG patterns during slow anesthesia induction. These patterns were partially identical to previous observations in humans, but also included significant differences, especially in the low frequencies. Our study emphasizes strengths and limitations of murine models in neuroscience and provides an important basis for future studies investigating complex neurophysiological mechanisms.

Incidence of postoperative acute kidney injury is twice as high in men than women following radical colorectal surgery — key findings from PROSACC, a posthoc analysis of a global, multicenter, randomized controlled trial

Acute kidney injury (AKI) affects approximately 8% of the general surgical population. Additionally, AKI increases the risk for morbidity and mortality by 8- and 3-fold respectively. It was earlier believed that women had a greater risk for postoperative AKI. However, recent literature indicates that the incidence of AKI is actually higher in hospitalized men than women (2.2 odds ratio). Hence the male sex is currently discussed to be a risk factor for AKI. We therefore hypothesized that the incidence of postoperative AKI will be higher amongst men than women after radical colorectal surgery. We conducted a posthoc analysis (PROSACC: Propofol or Sevoflurane Anesthesia in Colon Cancer, NCT05585866) on the database from the CAN-study (Cancer and Anesthesia: Survival After Radical Surgery, NCT01975064). The CAN-study included cancer patients undergoing radical surgery at several sites in China, Croatia, Poland, and Sweden. Patients included in PROSACC were those undergoing colorectal surgery at any predefined site. Primary outcome was incidence of AKI by changes in plasma creatinine, secondary outcome was AKI in association to gender (women/men). The KDIGO criteria was used for classifying AKI on postoperative days 1-3 and 4-10. Database management and statistical analysis was performed by Uppsala Research Centre. Men vs women AKI outcome at day 1-3 and 4-10 was statistically compared with the Pearson’s chi-square test. A total of 3254 patients (n=1900 men; n=1354 women) were included in the analysis with their preoperative plasma creatinine. Demographics showed that of the women, 39% had hypertension, 12% had diabetes and 2% had preexisting kidney disease. In comparison, amongst the men, 24% had hypertension, 9% had diabetes and 1% preexisting kidney disease. Postoperative plasma creatinine values were obtainable from the database in 2741 patients (n=1578 men; n=1163 women) on postoperative day 1-3. One hundred and ninety patients (7%) of this group had developed AKI. Separated by gender, 6% of the women (n=72) and 8% of the men (n=118) had established AKI according to KDIGO (p=0.190). Plasma creatinine values were obtainable in 986 patients (n=582 men; n=404 women) on postoperative day 4-10 whereas 87 patients (9%) in this group had developed AKI. Separated by gender, 6% of the women (n=23) but 11% of the men (n=64) had established AKI at this timepoint (p=0.004). With this posthoc analysis of a global, multicenter, randomized controlled trial we conclude that the incidence of postoperative AKI is twice as high in men compared with women after 4-10 postoperative days following radical colorectal surgery. Since the women had higher rate of pronounced preoperative risk factors yet still had lower incidence of AKI, this study aligns with the conclusion that the male sex is a risk factor for postoperative AKI. Funded by the Swedish Research Council (2014–02569 and 2014–07606). This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Effect of Continuous Infusion of Different Doses of Esketamine on the Bispectral Index During Sevoflurane Anesthesia: A Randomized Controlled Trial.

To investigate and quantify the effect of continuous esketamine infusion at different doses on the bispectral index (BIS) during sevoflurane anesthesia. A total of 120 patients scheduled for elective laparoscopic renal surgery were randomly divided into three groups. Under steady anesthesia and surgical situations, the patient was started on continuous infusion of the study drug: 0.125 mg/kg/h esketamine (group E1), 0.25 mg/kg/h esketamine (group E2), and the same volume of saline (group C). The primary outcome was changes in BIS value after 15 min (T15), 30 min (T30), 45 min (T45), and 60 min (T60) of drug infusion. The secondary outcomes were 95% spectral edge frequency (SEF95), electromyogram (EMG), heart rate (HR), and mean arterial pressure (MAP) from T0 to T60. Furthermore, postoperative pain, postoperative recovery, and perioperative adverse events were evaluated. Compared with group C, group E1 exhibited significant BIS elevation at T30-T60 and group E2 at T15-T60 (P < 0.001). Compared with group E1, group E2 showed a more significant BIS elevation at T15-T60 (P < 0.001). The area under the curve (AUC) of BIS and SEF95 were significantly higher in group E2 than in groups C and E1 (P < 0.05). BIS value for any of the three groups was significantly correlated with SEF95 (P < 0.001). No significant differences were observed in the AUC of EMG, HR, and MAP among the three groups. Intraoperative remifentanil consumption and postoperative NRS of pain on movement were significantly reduced in group E2 compared with groups C and E1 (P < 0.05). Continuous infusion of both 0.125 and 0.25 mg/kg/h of esketamine increased the BIS value during sevoflurane anesthesia, and the BIS value gradually stabilized with the prolongation of the infusion time.

A Comparative Study between Inhalation Anesthesia using Sevoflurane and Total Intravenous Anesthesia by Propofol in Patients with Elevated Liver Enzymes

A Comparative Study between Inhalation Anesthesia using Sevoflurane and Total Intravenous Anesthesia by Propofol in Patients with Elevated Liver Enzymes

Lidocaine effects on neutrophil extracellular trapping and angiogenesis biomarkers in postoperative breast cancer patients with different anesthesia methods: a prospective, randomized trial

BackgroundAnesthesia techniques and drug selection may influence tumor recurrence and metastasis. Neutrophil extracellular trapping (NETosis), an immunological process, has been linked to an increased susceptibility to metastasis in individuals with tumors. Furthermore, recurrence may be associated with vascular endothelial growth factor A (VEGF-A), a mediator of angiogenesis. This study investigates the impact of lidocaine (combined with sevoflurane or propofol anesthesia ) during breast cancer surgery inhibits the expression of biomarkers associated with metastasis and recurrence (specifically H3Cit, NE, MPO, MMP-9 and VEGF-A).MethodsWe randomly assigned 120 women undergoing primary or invasive breast tumor resection to receive one of four anesthetics: sevoflurane (S), sevoflurane plus i.v. lidocaine (SL), propofol (P), and propofol plus i.v. lidocaine (PL). Blood samples were collected before induction and 3 h after the operation. Biomarkers associated with NETosis (citrullinated histone H3 [H3Cit], myeloperoxidase [MPO], and neutrophil elastase [NE]) and angiogenesis were quantified using enzyme-linked immunosorbent assays.ResultsPatient and breast tumor characteristics, along with perioperative management, did not differ between study groups. In intra-group comparisons, S and P groups demonstrated a statistically significant increase in post-operative MPO (S group: 10.39[6.89–17.22] vs. 14.31[8.55–20.87] ng ml-1, P = 0.032; P group: 9.45[6.73–17.37] vs. 14.34[9.87–19.75] ng ml-1, P = 0.035)and NE(S group: 182.70[85.66-285.85] vs. 226.20[91.85-391.65] ng ml-1, P = 0.045; P group: 154.22[97.31–325.30] vs. 308.66[132.36-483.57] ng ml-1, P = 0.037) concentrations compared to pre-operative measurements, whereas SL and PL groups did not display a similar increase. H3Cit, MMP-9, and VEGF-A concentrations were not significantly influenced by the anesthesia techniques and drugs.ConclusionsRegardless of the specific technique employed for general anesthesia, there was no increase in the postoperative serum concentrations of MPO and NE after perioperative lidocaine infusion compared to preoperative serum concentrations. This supports the hypothesis that intravenous lidocaine during cancer surgery aimed at achieving a cure may potentially decrease the likelihood of recurrence. Further interpretation and discussion of clinical implications are warranted, emphasizing the significance of these findings in the context of cancer surgery and recurrence prevention.Clinical trial registrationChiCTR2300068563.

Investigation of the Effects of Hesperidin on Bisphenol-A Induced Neurotoxicity in Rats

Bisphenol A (BPA) is an adhesive substance used in the production of food packaging, electronic devices, dental sealants and polycarbonate plastics. This substance, which can leak into products during industrial processes, can be taken into the body through contact or consumption. BPA causes oxidative damage in the body and toxicity to organs. This study was conducted on 52 male rats. The rats were randomly distributed into 4 separate groups, with 13 animals in each. Experiment groups were formed as follows: Control: 1 ml of olive oil was administered intragastrically for 14 days. Hesperidin (HESP): HESP was administered intragastrically at a dose of 50 mg/kg for 14 days. BPA: BPA dissolved in olive oil was administered intragastrically at a dose of 100 mg/kg for 14 days. BPA+HESP: BPA at a dose of 100 mg/kg and HESP at a dose of 50 mg/kg were administered intragastrically for 14 days. Brain tissue samples from the rats were collected on the 15th day of the experiment while the rats were under sevoflurane anesthesia. Histopathological and biochemical analyzes were performed on the brain tissues of the rats. As a result of the study, it was observed that HESP had a protective effect on BPA-induced neurotoxicity in rats and triggered the antioxidant mechanism responsible for defense in the cell. It was opined that the degenerative and necrotic tissue damage caused by BPA in the brain tissue decreased with the effect of Hesperidin.

The effect of propofol-midazolam versus sevoflurane on bispectral index and eye position in pediatric cataract surgery: A randomized controlled study

ABSTRACT Background Cataract surgery is one of the infrequent ocular surgeries. The adequate ocular position with central alignment is the main prerequisite for good surgical technique. Propofol and sevoflurane are the common anesthetics drugs used during pediatric anesthesia. BIS monitor is one of the common intraoperative awareness monitors used. Aim To assess the efficacy of the bispectral index monitor in quantifying the depth of anesthesia and its correlation with ocular alignment during juvenile cataract surgery. Specifically, we will compare the use of sevoflurane anaesthesia with total intravenous anesthesia using a midazolam bolus and propofol infusion. Methods This study included 100 children scheduled for cataract surgery. The children were divided into two groups: group (S) included 50 children who were anesthetized using sevoflurane maintenance only and group (P) included 50 children who were anesthetized using continuous intravenous anesthesia (midazolam bolus plus propofol infusion) as maintenance after induction with sevoflurane anesthesia 8%. The bispectral index was recorded immediately after induction and after intubation and every 5 min later on until end of surgery. Results The eye position showed statistically significant central position among the propofol group with p value 0.02. An eye position-BIS value association was found statistically significant negative correlation in sevoflurane group while no statistically significant link was found in the propofol group. Conclusion Use of BIS monitor for making correlation between depth of anesthesia for prediction of ocular alignment was significant in sevoflurane group, but not in propofol group in pediatric patients and even with adequate depth of general anesthesia.

Relationship between intraoperative requirement for anesthetics and postoperative analgesic consumption in laparoscopic colectomy: a randomized controlled double-blinded study.

This study investigated the relationship between intraoperative requirement for an inhalational anesthetic (sevoflurane) or an opioid (remifentanil) and postoperative analgesic consumption. The study included 200 adult patients undergoing elective laparoscopic colectomy. In the sevoflurane group, the effect-site concentration of remifentanil was fixed at 1.0 ng/ml, while the inspiratory sevoflurane concentration was adjusted to maintain an appropriate anesthetic depth. In the remifentanil group, the end-expiratory sevoflurane concentration was fixed at 1.0 vol.%, and the remifentanil concentration was adjusted. Pain scores and cumulative postoperative analgesic consumptions were evaluated at 2, 6, 24, and 48 h after surgery. Average end-tidal concentration of sevoflurane and effect-site concentration of remifentanil were 2.0 ± 0.4 vol.% and 3.9 ± 1.4 ng/ml in the sevoflurane and remifentanil groups, respectively. Cumulative postoperative analgesic consumption at 48 h postoperatively was 55 ± 26 ml in the sevoflurane group and 57 ± 33 ml in the remifentanil group. In the remifentanil group, the postoperative cumulative analgesic consumptions at 2 and 6 h were positively correlated with intraoperative remifentanil requirements (2 h: r = 0.36, P < 0.001; 6 h: r = 0.38, P < 0.001). However, there was no significant correlation in the sevoflurane group (r = 0.04, P = 0.691). The amount of intraoperative requirement of short acting opioid, remifentanil, is correlated with postoperative analgesic consumption within postoperative 6 h. It may be contributed by the development of acute opioid tolerance. However, intraoperative sevoflurane requirement had no effect on postoperative analgesic consumption.

Activity of the Sodium Leak Channel Maintains the Excitability of Paraventricular Thalamus Glutamatergic Neurons to Resist Anesthetic Effects of Sevoflurane in Mice.

Stimulation of the paraventricular thalamus has been found to enhance anesthesia recovery; however, the underlying molecular mechanism by which general anesthetics modulate paraventricular thalamus is unclear. This study aimed to test the hypothesis that the sodium leak channel (NALCN) maintains neuronal activity in the paraventricular thalamus to resist anesthetic effects of sevoflurane in mice. Chemogenetic and optogenetic manipulations, in vivo multiple-channel recordings, and electroencephalogram recordings were used to investigate the role of paraventricular thalamus neuronal activity in sevoflurane anesthesia. Virus-mediated knockdown and/or overexpression was applied to determine how NALCN influenced excitability of paraventricular thalamus glutamatergic neurons under sevoflurane. Viral tracers and local field potentials were used to explore the downstream pathway. Single neuronal spikes in the paraventricular thalamus were suppressed by sevoflurane anesthesia and recovered during emergence. Optogenetic activation of paraventricular thalamus glutamatergic neurons shortened the emergence period from sevoflurane anesthesia, while chemogenetic inhibition had the opposite effect. Knockdown of the NALCN in the paraventricular thalamus delayed the emergence from sevoflurane anesthesia (recovery time: from 24 ± 14 to 64 ± 19 s, P < 0.001; concentration for recovery of the righting reflex: from 1.13% ± 0.10% to 0.97% ± 0.13%, P < 0.01). As expected, the overexpression of the NALCN in the paraventricular thalamus produced the opposite effects. At the circuit level, knockdown of the NALCN in the paraventricular thalamus decreased the neuronal activity of the nucleus accumbens, as indicated by the local field potential and decreased single neuronal spikes in the nucleus accumbens. Additionally, the effects of NALCN knockdown in the paraventricular thalamus on sevoflurane actions were reversed by optical stimulation of the nucleus accumbens. Activity of the NALCN maintains the excitability of paraventricular thalamus glutamatergic neurons to resist the anesthetic effects of sevoflurane in mice.

Translatome and transcriptome profiling of neonatal mice hippocampus exposed to sevoflurane anesthesia

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.

Comparison of the Effects of Inhalational Anesthesia with Sevoflurane and Total Intravenous Anesthesia in Open Heart Surgery

Background: The primary objective of this study was to compare sevoflurane inhalation anesthesia with total intravenous anesthesia (TIVA) in terms of its effectiveness in maintaining adequate depth of anesthesia during all open heart surgery procedures, including cardiopulmonary bypass. The study's secondary objective was to compare sevoflurane inhalation anesthesia with TIVA regarding the impact on the time of tracheal extubation and the incidence of postoperative acute kidney injury during open heart surgeries. Methods: A total of 58 patients undergoing open heart surgery were included, with 30 receiving sevoflurane inhalation anesthesia and 28 receiving TIVA. Demographic characteristics, intraoperative parameters, and postoperative outcomes were recorded and analyzed. Statistical analysis revealed no significant differences in Bispectral Index (BIS) monitor values, mean arterial pressure, body temperature, or other intraoperative parameters between the two groups. Notably, the time to tracheal extubation was significantly shorter in the Sevoflurane group compared to the TIVA group, although both groups exhibited similar rates of postoperative acute kidney injury (AKI). Results: None of the patients had complaints of intraoperative awareness. The mean arterial pressure, body temperature, and bispectral index values during and before cardiopulmonary bypass were similar between the groups. Postoperative variables such as intensive care unit stay duration, incidence of acute kidney injury, and immediate and 24-hour post-extubation visual analog scale values were similar between the groups. The tracheal extubation time was found to be statistically shorter in the sevoflurane group. Conclusion: We believe that sevoflurane inhalation anesthesia can achieve adequate depth of anesthesia during the intraoperative period in open heart surgery without increasing the rate of postoperative complications.

Effect of Dexmedetomidine Combined with Remifentanil on Emergence Agitation During Awakening from Sevoflurane Anesthesia for Pediatric Liver Surgery.

BACKGROUND We aimed to assess the effect of dexmedetomidine (Dex) combined with remifentanil on emergence agitation (EA) during awakening from sevoflurane anesthesia for pediatric liver surgery. MATERIAL AND METHODS Sixty children who underwent liver surgery in our hospital were prospectively selected and randomly allocated into group A (placebo+remifentanil+sevoflurane) or group B (Dex+remifentanil+sevoflurane). Mean arterial pressure (MAP) and heart rate (HR) at different time points, agitation score during awakening, behavioral status, pain level, and the incidence of postoperative adverse effects were compared in both groups. RESULTS Children in group B had lower HR and MAP levels immediately after tracheal extubation and 5 min after tracheal extubation than those in group A. The Aono's scores, PAED agitation scores, and CHIPP scores at 15 min and 30 min of admission to the PACU were lower in group B than in group A. The incidence of agitation during postoperative anesthesia awakening was lower in group B in contrast to group A. There was no significant difference in postoperative adverse reactions between group A and group B. CONCLUSIONS In pediatric liver surgery, the use of Dex+remifentanil+sevoflurane anesthesia can reduce the incidence of EA during the awakening period, stabilize hemodynamic levels, and relieve postoperative pain, and has fewer postoperative adverse effects, which warrants clinical application.

Nicardipine constant rate infusion alleviates the cardiovascular effects of dexmedetomidine infusions without affecting the minimal alveolar concentration in sevoflurane-anesthetized dogs

Two randomized crossover trials evaluated the effects of nicardipine constant rate infusion (CRI) on 1) the anesthetic potency of sevoflurane and 2) the ability to attenuate dexmedetomidine-induced cardiovascular depression in anesthetized dogs. First, six healthy Beagle dogs weighing 11.7 ± 0.9 kg were allocated to one of three treatments that administered a CRI of carrier (saline) or dexmedetomidine 0.5 or 3.0 μg/kg/h following a loading dose. The minimum alveolar concentration (MAC) of sevoflurane was determined utilizing electric stimuli before and after the loading dose of nicardipine (20 μg/kg intravenously for 10 min), followed by CRI at 40 μg/kg/h with 60 min of equilibration. Subsequently, cardiovascular and blood gas variables were evaluated in another trial under sevoflurane anesthesia at the individual 1.5 MAC. After baseline measurements, the dogs were assigned to two treatments (dexmedetomidine CRI at 0.5 or 3.0 μg/kg/h following a loading dose) with sevoflurane doses adjusted to 1.5 times of MAC equivalent, and the measurements were repeated every 15 min for 120 min. After 60 min, nicardipine CRI at 40 μg/kg/h with a loading dose was added to the dexmedetomidine CRI. Dexmedetomidine infusions significantly decreased the sevoflurane MAC but nicardipine did not significantly alter the MAC either with or without dexmedetomidine CRI in dogs. Dexmedetomidine dose-dependently decreased the cardiac index and increased the systemic vascular resistance index; these effects were fully counteracted by concomitant nicardipine CRI. Nicardipine CRI can be useful for controlling the cardiovascular depression elicited by dexmedetomidine in anesthetized dogs without affecting the anesthetic potency of sevoflurane.

Damage-associated molecular patterns as a mechanism of sevoflurane-induced neuroinflammation in neonatal rodents.

General anesthesia is inevitable for pediatric patients undergoing surgery, though volatile anesthetic agents may cause neuroinflammation and neurodevelopmental impairment; however, the underlying pathophysiology remains unclear. We aimed to investigate the neuroinflammation mechanism in developing rat brains associated with sevoflurane exposure time, by identifying the specific damage-associated molecular patterns (DAMPs) pathway and evaluating the effects of non-steroidal anti-inflammatory drugs (NSAIDs) in alleviating neuroinflammation. A three-step experiment was conducted to investigate neuroinflammation induced by sevoflurane. First, the exposure time required for sevoflurane to cause neuroinflammation was determined. Next, the specific pathways of DAMPs involved in neuroinflammation by sevoflurane were identified. Finally, the effects of NSAIDs on sevoflurane-induced neuroinflammation were investigated. The expression of various molecules in the rat brain were assessed using immunohistochemistry, immunofluorescence, quantitative real-time polymerase chain reaction, western blot analysis, and enzyme-linked immunosorbent assay. In total, 112 rats (aged 7 days) were used, of which six rats expired during the experiment (mortality rate, 5.3%). Expression of CD68, HMGB-1, galectin-3, TLR4, TLR9, and phosphorylated NF-κB was significantly increased upon 6 h of sevoflurane exposure. Conversely, transcriptional levels of TNF-α and IL-6 significantly increased and IFN-γ significantly decreased after 6 h of sevoflurane exposure. Co-administration of NSAIDs with sevoflurane anesthesia significantly attenuated TNF-α and IL-6 levels and restored IFN-γ levels. In conclusion, 6 h of sevoflurane exposure induces neuroinflammation through the DAMPs pathway, HMGB-1, and galectin-3. Co-administration of ibuprofen reduced sevoflurane-induced neuroinflammation.

Effect of South Sulawesi Propolis in Sevoflurane Anesthesia-Induced Rat Model During Weaning Period: Study Levels of IL-6, TNF⍺, IL-10, and PSD-95 of the Prefrontal Cortex

Background: A recent study discovered that exposure to the anesthetic gas sevoflurane in the early years of life can impact cognitive function. Objectives: This study aims to investigate the effects of prolonged and repeated exposure to sevoflurane during the weaning period and whether the administration of propolis, a well-known herbal substance with anti-inflammatory properties, has a beneficial effect on inflammation and synaptic markers of the prefrontal cortex area, as well as its effect on spatial working memory function. Methods: We utilized Sprague Dawley rats aged 21 days (P21), divided into three groups: Control, sevoflurane, and sevoflurane with propolis. The exposure to sevoflurane (3%) was conducted three times for 2 hours each at P21, P23, and P25. Propolis treatments were administered orally, starting from the first day of exposure to sevoflurane until the rats were sacrificed (P25 or P51). Analyses of IL-6, TNF-alpha, IL-10, PSD-95 levels were performed using ELISA at P25 and P51, while spatial working memory was measured using the spontaneous Y-maze at P51. Results: Exposure to sevoflurane during the weaning period had no effect on IL-6, TNF-alpha, IL-10, and PSD-95 levels of the prefrontal cortex, nor on working memory function. Similarly, the administration of propolis did not have any beneficial effect on these parameters. Conclusions: Prolonged and repeated exposure to sevoflurane during the weaning period did not induce neuroinflammation conditions that also did not affect synaptic markers and working memory function. Further studies are required to identify a dose of sevoflurane that causes detrimental effects on memory function, neuroinflamation and synaptic marker and further to explore the beneficial effects of propolis on this condition.

Comparing the Efficacy of Various Anaesthesia Protocols for Caesarean Section in Dogs

Introduction. Caesarean section is attributed with frequent deaths among newborn puppies – up to 30%, depending on the chosen anaesthetic care and the presence of aggravating factors. The right choice of drugs and anaesthetic techniques can significantly affect the clinical outcomes. Because a standardised anaesthesia protocol for the caesarean section in dogs is missing in Russia, the research in this area is very relevant. The aim of the work is to compare three variants of the anaesthesia protocols across the basic clinical outcomes of a caesarean section delivery in a dog (including intra- and postoperative results, mortality rate) and to determine the most efficient and safe one for a bitch and puppies.Materials and Methods. The research was conducted at the premises of Rostov-on-Don veterinary clinic in the period from December 2021 to December 2023. There were selected 63 pregnant bitches who met the inclusion and exclusion criteria at that period of time. The animals were divided into three groups: in the first group the anaesthetic care included induction with propofol, intraoperative inhalation anaesthesia with sevoflurane and epidural lidocaine anaesthesia; in the second group the induction and maintenance of anaesthesia was performed with propofol, alongside the local anaesthesia with lidocaine was administered; the third group was administered propofol and inhalation anaesthesia with sevoflurane, excluding epidural anaesthesia. Monitoring was carried out according to the intraoperative indicators, post-anaesthesia recovery time, postoperative indicators of fear and pain, Apgar scores in puppies, the number of survivors and deaths in the short-term (30 minutes) and medium-term (during the day) periods.Results. The best intra- and postoperative indicators as well as the highest percentage of surviving puppies and the smallest number of stillbirths were revealed in patients of the first group. Medium results were recorded in the third group. The lowest intraoperative indicators in the function of cardiovascular and respiratory systems and the worst results as of hypoxia in newborn puppies were recorded in the second group of studied animals.Discussion and Conclusion. When determining the most efficient anaesthetic care for caesarean section in dogs, it should be borne in mind that propofol has a depressing effect on the respiratory and cardiovascular systems of patients, therefore its use is highly undesirable for the anaesthesia maintenance. Unlike propofol, sevoflurane does not penetrate the placenta barrier, is not metabolised and enables quick awakening of a bitch from anaesthesia. Moreover, in cases, when sevoflurane was used, the Apgar scores in the born puppies were the highest. Epidural anaesthesia with lidocaine reduces the postoperative pain of a bitch after caesarean section and has a positive effect on lactation. The use of epidural anaesthesia may be complicated with hypotension, however, the preventive use of crystalloid solutions, can mitigate this effect. Thus, the protocol with triple anaesthesia is optimal and preferable for caesarean section in dogs: induction with propofol, epidural anaesthesia with lidocaine and inhalation with sevoflurane to maintain anaesthesia.