Prolonged Sevoflurane Anesthesia Research Articles

Astrocyte-derived exosomes-transported miRNA-26a-5p ameliorates sevoflurane-induced cognitive dysfunction in aged mice

Prolonged sevoflurane anesthesia is the primary factor contributing to the development of perioperative neurocognitive disorders (PND). Recent studies have highlighted neuronal apoptosis and abnormal dendritic structures as crucial features of PND. Astrocytes-derived exosomes (ADEs) have been identified as carriers of microRNAs (miRNAs), playing a vital role in cell-to-cell communication through transmitting genetic material. Nevertheless, the specific mechanisms by which miRNAs in ADEs contribute to sevoflurane-induced cognitive deficit are currently unknown. Through a series of in vivo and in vitro experiments, we demonstrated that ADEs contributed to improved neurocognitive outcomes by reducing neuronal apoptosis and promoting dendritic development. Our miRNA microarray analysis revealed a significant increase in the expression level of miR-26a-5p within ADEs. Furthermore, we identified NCAM as the downstream target gene of miR-26a-5p. Subsequent gain- and loss-of-function experiments were conducted to validate the role of the miR-26a-5p/NCAM axis. Finally, we found that the AKT/GSK3-β/CRMP2 signaling pathway was involved in regulating neurons through exosomal miR-26a-5p. Taken together, our findings suggest that the treatment with miR-26a-5p in ADEs can improve neurocognitive outcomes induced by long-term sevoflurane anesthesia, suggesting a promising approach for retarding the progress of PND.

Propofol and Sevoflurane Anesthesia in Early Childhood Do Not Influence Seizure Threshold in Adult Rats.

Experimental studies have demonstrated that general anesthetics administered during the period of synaptogenesis may induce widespread neurodegeneration, which results in permanent cognitive and behavioral deficits. What remains to be elucidated is the extent of the potential influence of the commonly used hypnotics on comorbidities including epilepsy, which may have resulted from increased neurodegeneration during synaptogenesis. This study aimed to test the hypothesis that neuropathological changes induced by anesthetics during synaptogenesis may lead to changes in the seizure threshold during adulthood. Wistar rat pups were treated with propofol, sevoflurane, or saline on the sixth postnatal day. The long-term effects of prolonged propofol and sevoflurane anesthesia on epileptogenesis were assessed using corneal kindling, pilocarpine-, and pentylenetetrazole-induced seizure models in adult animals. Body weight gain was measured throughout the experiment. No changes in the seizure threshold were observed in the three models. A significant weight gain after exposure to anesthetics during synaptogenesis was observed in the propofol group but not in the sevoflurane group. The results suggest that single prolonged exposure to sevoflurane or propofol during synaptogenesis may have no undesirable effects on epileptogenesis in adulthood.

Cdh1-Mediated Metabolic Switch from Pentose Phosphate Pathway to Glycolysis Contributes to Sevoflurane-Induced Neuronal Apoptosis in Developing Brain.

Cdh1 is a regulatory subunit of the anaphase promoting complex/cyclosome (APC/C), known to be involved in regulating neuronal survival. The role of Cdh1 in volatile anesthetics-induced neuronal apoptosis in the developing brain is unknown. In this study, we used postnatal day 7 (P7) and day 21 (P21) mice exposed to 2.3% sevoflurane for 6 h to investigate at which age and duration of exposure sevoflurane affects the expression of Cdh1 and glycolytic enzyme 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 3 (PFKFB3) and that of the pentose phosphate pathway (PPP) enzyme, glucose-6-phosphate dehydrogenase (G6PD). Furthermore, we tested whether the cyclin-dependent kinases (cdks) inhibitor roscovatine could counteract the effects caused by exposure to sevoflurane. Finally, we applied the glycolysis inhibitor 3-(3-pyridinyl)-1-(4-pyridinyl)-2-propen-1-one (3-PO), G6PD inhibitor dehydroepiandrosterone (DHEA), and exogenous reduced glutathione to examine the contribution of the glycolysis pathway and PPP to sevoflurane-induced neuroapoptosis. We found that prolonged sevoflurane anesthesia significantly reduces the Cdh1 level in P7 mice compared to in the P21 ones; moreover, the decrease in Cdh1 level results in a switch in glucose metabolism from the PPP to neuronal glycolysis. This leads to an imbalance between reactive oxygen species production and reduced glutathione level in the developing brain, which is more susceptible to oxidative stress. As a result, sevoflurane induces neuroapoptosis through Cdh1-mediated glucose metabolism reprogramming. Our study demonstrates a critical role of Cdh1 in sevoflurane-induced neuroapoptosis by shifting PPP to the glycolytic pathway in the developing brain. These findings suggest that Cdh1 may be a novel target for preventing volatile anesthetics-induced neurotoxicity and memory impairment.

Potential Effect of Prolonged Sevoflurane Anesthesia on the Kinetics of [11C]Raclopride in Non-human Primates

PurposePositron emission tomography (PET) in non-human primates (NHP) is commonly performed under anesthesia, with sevoflurane being a widely used inhaled anesthetic. PET measurement in NHP can be repeated, and a difference in radioligand kinetics has previously been observed between the first and second PET measurement on the same day using sevoflurane anesthesia. In this study, we evaluated the effect of prolonged sevoflurane anesthesia on kinetics and binding potential (BPND) of [11C]raclopride in NHP.ProceduresThree cynomolgus monkeys underwent two to three PET measurements with [11C]raclopride under continuous sevoflurane anesthesia on the same day. The concentration of sevoflurane was adjusted according to the general conditions and safety parameters of the NHP. Time to peak (TTP) radioactivity in the striatum was estimated from time-activity curves (TACs). The BPND in the striatum was calculated by the simplified reference tissue model using the cerebellum as reference region.ResultsIn each NHP, the TTP became shorter in the later PET measurements than in the first one. Across all measurements (n = 8), concentration of sevoflurane correlated with TTP (Spearman’s ρ = − 0.79, p = 0.03), but not with BPND (ρ = − 0.25, p = 0.55).ConclusionsThese data suggest that sevoflurane affects the shape of TACs but has no evident effect on BPND in consecutive PET measurements.

The Effects of Prolonged Low-Flow Sevoflurane Anesthesia on Renal and Hepatic Function

The Effects of Prolonged Low-Flow Sevoflurane Anesthesia on Renal and Hepatic Function

Renal Function in Patients with High Serum Fluoride Concentrations After Prolonged Sevoflurane Anesthesia

BACKGROUND In studies of methoxyflurane-induced nephrotoxicity, renal-concentrating impairment has been observed only when serum inorganic fluoride concentrations exceed 50 microM. Prolonged sevoflurane anesthesia can result in serum inorganic fluoride concentrations in excess of 50 microM. The authors compared renal function after prolonged sevoflurane anesthesia with that after isoflurane anesthesia. In addition, they measured urinary excretion of N-acetyl-beta-glucosaminidase (NAG), a sensitive index of renal tubular damage, during the 3-day period after anesthesia. METHODS Thirty-four healthy patients who underwent either sevoflurane (23 patients) or isoflurane (11 patients) anesthesia at a total gas flow of 61/min for orthopedic surgery scheduled to last at least 5 h were studied. At 16.5 h after cessation of anesthesia, patients were administered 10 units of vasopressin and urine was collected frequently thereafter for evaluation of urinary osmolality. In addition, urinary excretion of NAG was measured before and on days 1-3 after anesthesia. Based on whether peak fluoride concentrations exceeded 50 microM, 23 patients anesthetized with sevoflurane were assigned to a sevofluranehigh group (> 50 microM) or a sevofluranelow (< 50 microM) group. RESULTS The eight patients in the sevofluranehigh group had a mean peak fluoride concentration of 57.5 +/- 4.3 microM. A significant, albeit weak, inverse correlation was found between peak fluoride concentration and maximal urinary osmolality after the injection of vasopressin (r = -0.42, P < 0.05). Mean maximum urinary osmolality tended to be lower in the sevofluranehigh group (681 +/- 60 mOsm/kg) than in the other two groups after administration of vasopressin, although the difference among the three groups did not quite reach a statistical significance (P = 0.068). One patient had a transient concentrating defect (maximum urinary osmolality = 390 mOsm/kg) on day 1 after anesthesia. Urinary excretion of NAG in both the sevofluranehigh and sevofluranelow groups was greater on days 2 and 3 after anesthesia than before anesthesia. The increase in urinary NAG excretion was dose related with sevoflurane, but there was no difference in results of routine laboratory renal tests on days 2 and 3 after anesthesia among the three groups. CONCLUSIONS The authors concluded that sevoflurane anesthesia results in increased serum fluoride concentration, a tendency toward decreased maximal ability to concentrate urine, and increased excretion of NAG. However, the increase in urinary NAG excretion was not indicative of clinically significant renal damage in these patients with no preexisting renal disease.

The Study for Renal Effects of Increased Serum and Urinary Inorganic Fluoride Levels after Prolonged Sevoflurane Anesthesia

The Study for Renal Effects of Increased Serum and Urinary Inorganic Fluoride Levels after Prolonged Sevoflurane Anesthesia

Renal Function in Patients with High Serum Fluoride Concentrations after Prolonged Sevoflurane Anesthesia

In studies of methoxyflurane-induced nephrotoxicity, renal-concentrating impairment has been observed only when serum inorganic fluoride concentrations exceed 50 microM. Prolonged sevoflurane anesthesia can result in serum inorganic fluoride concentrations in excess of 50 microM. The authors compared renal function after prolonged sevoflurane anesthesia with that after isoflurane anesthesia. In addition, they measured urinary excretion of N-acetyl-beta-glucosaminidase (NAG), a sensitive index of renal tubular damage, during the 3-day period after anesthesia. Thirty-four healthy patients who underwent either sevoflurane (23 patients) or isoflurane (11 patients) anesthesia at a total gas flow of 61/min for orthopedic surgery scheduled to last at least 5 h were studied. At 16.5 h after cessation of anesthesia, patients were administered 10 units of vasopressin and urine was collected frequently thereafter for evaluation of urinary osmolality. In addition, urinary excretion of NAG was measured before and on days 1-3 after anesthesia. Based on whether peak fluoride concentrations exceeded 50 microM, 23 patients anesthetized with sevoflurane were assigned to a sevofluranehigh group (> 50 microM) or a sevofluranelow (< 50 microM) group. The eight patients in the sevofluranehigh group had a mean peak fluoride concentration of 57.5 +/- 4.3 microM. A significant, albeit weak, inverse correlation was found between peak fluoride concentration and maximal urinary osmolality after the injection of vasopressin (r = -0.42, P < 0.05). Mean maximum urinary osmolality tended to be lower in the sevofluranehigh group (681 +/- 60 mOsm/kg) than in the other two groups after administration of vasopressin, although the difference among the three groups did not quite reach a statistical significance (P = 0.068). One patient had a transient concentrating defect (maximum urinary osmolality = 390 mOsm/kg) on day 1 after anesthesia. Urinary excretion of NAG in both the sevofluranehigh and sevofluranelow groups was greater on days 2 and 3 after anesthesia than before anesthesia. The increase in urinary NAG excretion was dose related with sevoflurane, but there was no difference in results of routine laboratory renal tests on days 2 and 3 after anesthesia among the three groups. The authors concluded that sevoflurane anesthesia results in increased serum fluoride concentration, a tendency toward decreased maximal ability to concentrate urine, and increased excretion of NAG. However, the increase in urinary NAG excretion was not indicative of clinically significant renal damage in these patients with no preexisting renal disease.

Sevoflurane degradation product concentrations with soda lime during prolonged anesthesia

Study Objectives: To evaluate the decomposition of sevoflurane in soda lime during prolonged sevof lurane anesthesia in humans. To evaluate for evidence of renal or hepatotoxicity as a result of exposure to these sevoflurane degradation compounds. Design: Prospective evaluation in healthy volunteers. Setting: Clinical research unit and postanesthesia care unit of a university hospital. Patients: Six healthy male volunteers. Interventions: Subjects were anesthetized with sevoflurane 1 to 1.2 minimum alveolar concentration for greater than 9 hours with a semiclosed circuit anesthetic technique (5-liter total flow) with fresh soda lime as the absorbent. Measurements and Main Results: Laboratory tests of renal and hepatic function were performed before anesthesia and 1 and 5 days after anesthesia. During sevoflurane anesthesia, inhalation and exhalation circuit limb gas samples were obtained for degradation compound analysis. Only one degradation product, fluoromethyl-2,2-difluoro-l-(trifluoromethyl) vinyl ether (compound A), was detected. Inhalation concentration was maximal (7.6 ± 1.0 ppm) at 2 hours and did not increase further after this time point. There were no differences in preanesthesia and postanesthesia tests of hepatic and renal function. Conclusions:Levels of the degradation compound (compound A) produced in semiclosed circuit sevoflurane anesthesia with soda lime are well below potential toxic levels and thus appear safe. When sevoflurane is administered under these conditions for prolonged anesthesia, concentrations of compound A do not continue to increase throughout anesthesia.