Inhalation Anesthetics Isoflurane Research Articles

The genotoxicity effects and oxidative stress of common volatile and injectable anesthesia drugs on peripheral blood during irradiation of BALB/c mice

IntroductionIonizing radiation (IR) is well-known for its genotoxic and cytotoxic effects. Additionally, anesthesia has been shown to cause various side effects, including genotoxicity. This study aims to evaluate the DNA damage and oxidative stress resulting from exposure to both anesthesia and IR. MethodsSeventy BALB/c male mice were divided into 14 identical groups and anesthetized using three different inhalation anesthetics (isoflurane, sevoflurane, and halothane) and three different injectable anesthetics (propofol, ketamine, and thiopental). We also evaluated combinations of these anesthetic drugs with 1 Gy IR. DNA damage in white blood cells was assessed using the alkaline comet assay at 0, 2, and 24 h after treatment. Additionally, oxidative stress in blood samples was measured 6 h post-treatment. ResultsThe percentage of DNA in the tail and fragmented nuclei after 2 and 24 h was significantly higher in the groups given volatile anesthetics compared to the propofol and thiopental groups (P<0.05). Furthermore, oxidative stress levels were also significantly higher in the volatile anesthetic groups (P<0.05). When combined with IR, the volatile anesthetics and ketamine resulted in increased genotoxicity and significantly higher oxidative stress compared to the group exposed only to IR (P<0.05). In contrast, propofol and thiopental did not lead to a significant increase in genotoxicity or oxidative stress compared to the control group (P>0.07). ConclusionCombining volatile anesthetic drugs and ketamine with 1 Gy irradiation resulted in higher levels of toxic effects and oxidative stress, although this combination did not produce a synergistic effect. Additionally, the combination of propofol and thiopental with IR did not show a significant difference compared to the irradiated-only group in both the alkaline comet and oxidative stress assays.

Age-Related Effects of Inhalational Anesthetics in B4galnt1-Null and Cuprizone-Treated Mice: Clinically Relevant Insights into Demyelinating Diseases.

Anesthetics are essential agents that are frequently used in clinical practice to induce a reversible loss of consciousness and sensation by depressing the central nervous system. The inhalational anesthetics isoflurane and sevoflurane are preferred due to their rapid induction and recovery times and ease of administration. Despite their widespread use, the exact molecular mechanisms by which these anesthetics induce anesthesia are not yet fully understood. In this study, the age-dependent effects of inhalational anesthetics on two demyelination models were investigated: congenital (B4galnt1-null) and chemically induced (cuprizone). Various motor and cognitive tests were used to determine sensitivity to isoflurane and sevoflurane anesthesia. B4galnt1-null mice, which exhibit severe motor deficits due to defects in ganglioside synthesis, showed significant impairments in motor coordination and balance in all motor tests, which were exacerbated by both anesthetics. Cuprizone-treated mice, which mimic the demyelination in B4galnt1-null mice, also showed altered, age-dependent sensitivity to anesthesia. The study showed that older mice exhibited more pronounced deficits, with B4galnt1-null mice showing the greatest susceptibility to sevoflurane. These differential responses to anesthetics suggest that age and underlying myelin pathology significantly influence anesthetic effects.

Isoflurane-induced neuroinflammation and NKCC1/KCC2 dysregulation result in long-term cognitive disorder in neonatal mice

BackgroundThe inhalational anesthetic isoflurane is commonly utilized in clinical practice, particularly in the field of pediatric anesthesia. Research has demonstrated its capacity to induce neuroinflammation and long-term behavioral disorders; however, the underlying mechanism remains unclear [1]. The cation-chloride cotransporters Na+–K+–2Cl−–1 (NKCC1) and K+–2Cl−–2 (KCC2) play a pivotal role in regulating neuronal responses to gamma-aminobutyric acid (GABA) [2]. Imbalances in NKCC1/KCC2 can disrupt GABA neurotransmission, potentially leading to neural circuit hyperexcitability and reduced inhibition following neonatal exposure to anesthesia [3]. Therefore, this study postulates that anesthetics have the potential to dysregulate NKCC1 and/or KCC2 during brain development.MethodsWe administered 1.5% isoflurane anesthesia to neonatal rats for a duration of 4 h at postnatal day 7 (PND7). Anxiety levels were assessed using the open field test at PND28, while cognitive function was evaluated using the Morris water maze test between PND31 and PND34. Protein levels of NKCC1, KCC2, BDNF, and phosphorylated ERK (P-ERK) in the hippocampus were measured through Western blotting analysis. Pro-inflammatory cytokines IL-1β, IL-6, and TNF-α were quantified using ELISA.ResultsWe observed a decrease in locomotion trajectories within the central region and a significantly shorter total distance in the ISO group compared to CON pups, indicating that isoflurane induces anxiety-like behavior. In the Morris water maze (MWM) test, rats exposed to isoflurane exhibited prolonged escape latency onto the platform. Additionally, isoflurane administration resulted in reduced time spent crossing in the MWM experiment at PND34, suggesting long-term impairment of memory function. Furthermore, we found that isoflurane triggered activation of pro-inflammatory cytokines IL-1β, IL-6, and TNF-α; downregulated KCC2/BDNF/P-ERK expression; and increased the NKCC1/KCC2 ratio in the hippocampus of PND7 rats. Bumetadine (NKCC1 specific inhibitors) reversed cognitive damage and effective disorder induced by isoflurane in neonatal rats by inhibiting TNF-α activation, normalizing IL-6 and IL-1β levels, restoring KCC2 expression levels as well as BDNF and ERK signaling pathways. Based on these findings, it can be speculated that BDNF, P-ERK, IL-1β, IL-6 and TNF - α may act downstream of the NKCC1/KCC2 pathway.ConclusionsOur findings provide evidence that isoflurane administration in neonatal rats leads to persistent cognitive deficits through dysregulation of the Cation-Chloride Cotransporters NKCC1 and KCC2, BDNF, p-ERK proteins, as well as neuroinflammatory processes.

Higher Brain Uptake of Gentamicin and Ceftazidime under Isoflurane Anesthesia Compared to Ketamine/Xylazine.

We have recently shown that the volatile anesthetics isoflurane and sevoflurane acutely enhance the brain uptake of the hydrophilic markers sucrose and mannitol about two-fold from an awake condition, while the combined injection of the anesthetic agents ketamine and xylazine has no effect. The present study investigated two small-molecule hydrophilic drugs with potential neurotoxicity, the antibiotic agents ceftazidime and gentamicin. Transport studies using an in vitro blood-brain barrier (BBB) model, a monolayer of induced pluripotent stem cell-derived human brain microvascular endothelial cells seeded on Transwells, and LC-MS/MS analysis demonstrated the low permeability of both drugs in the range of sucrose, with permeability coefficients of 6.62 × 10-7 ± 2.34 × 10-7 cm/s for ceftazidime and 7.38 × 10-7 ± 2.29 × 10-7 cm/s for gentamicin. In vivo brain uptake studies of ceftazidime or gentamicin after IV doses of 25 mg/kg were performed in groups of 5-6 mice anesthetized at typical doses for surgical procedures with either isoflurane (1.5-2% v/v) or ketamine/xylazine (100:10 mg/kg I.P.). The brain uptake clearance, Kin, for ceftazidime increased from 0.033 ± 0.003 μL min-1 g-1 in the ketamine/xylazine group to 0.057 ± 0.006 μL min-1 g-1 in the isoflurane group (p = 0.0001), and from 0.052 ± 0.016 μL min-1 g-1 to 0.101 ± 0.034 μL min-1 g-1 (p = 0.0005) for gentamicin. We did not test the dose dependency of the uptake, because neither ceftazidime nor gentamicin are known substrates of any active uptake or efflux transporters at the BBB. In conclusion, the present study extends our previous findings with permeability markers and suggests that inhalational anesthetic isoflurane increases the BBB permeability of hydrophilic small-molecule endobiotics or xenobiotics when compared to the injection of ketamine/xylazine. This may be of clinical relevance in the case of potential neurotoxic substances.

Influência sobre valores de bioquímica clínica de saguis-de-tufo-preto (Callithrix penicillata) anestesiados com isoflurano ou sevoflurano

ABSTRACT The objective of this study was to evaluate the clinical biochemistry behavior of Black-Tufted Marmosets (Callithrix penicillatta) submitted to blood collection without sedation and after general anesthesia with anesthetics isoflurane or sevoflurane. Blood collections were performed on (M1) day before anesthesia by physical restraint, and (M2) after anesthesia. There were four groups: Isoflurane (GI) and Sevoflurane (GS) using an anesthetic box. GIM: isoflurane induction with mask for a shorter period. Control group (GP): physical restraint in both moments. Plasma was separated and frozen to measure clinic biochemistry values. Urea was higher at M2 in groups GI and GP. AST was higher in M2 in GI, GS, and GP and only GI showed an increase in CK in M2. Glucose was higher in M1 in the GI, GS, and GP groups and fructosamine was higher in M2 in the GI. Stress caused by physical restraint can cause biochemical changes and these must be considered when interpreting the exams. Both the inhalational anesthetic isoflurane and sevoflurane did not cause clinically significant changes in clinical biochemistry results.

Changes in the gas composition and acid-base state of blood during cesarean section in dogs with various methods of general anesthesia

The purpose of the studies was to compare and evaluate the effect of different anesthesia protocols for operative delivery in dogs. The studies were performed on 60 pregnant females of different breeds aged 2 to 6 years, with an average weight of 22 ±4.6 kg. Animals were divided into three groups, 20 in each. Animals of the first group for the introduction and maintenance of general anesthesia used Propofol at a dose of 4-6 mg/kg. Animals of the second and third groups were introduced into anesthesia using inhalation anesthetics through a mask, then tracheal intubation was performed and general anesthesia was maintained by an anesthetic-respiratory apparatus. In the second group, Isoflurane 0.5 - 2.0 vol% was used as the main anesthetic; in the third group, Sevoflurane 1.0 - 2.0 vol%. Sevoflurane had the least impact, minimally deviating the studied parameters from the original data. The greatest changes were always observed when administered to anesthesia, manifesting as moderate and severe hypoxemia and hypercapnia. Analyzing the data obtained, we concluded that the use of inhalation anesthetics isoflurane and, in particular, sevoflurane, during caesarean section is preferable due to their less pronounced effect on gas composition and acid-base blood composition.

MODERN ASPECTS IN ANESTHESIA OF SMALL LABORATORY ANIMALS

Experiments with small laboratory animals are required for better understanding of a disease flow, for studying the mechanisms of it’s development and for the development of new therapeutic strategies. A significant part of experimental studies involve anesthesia. In this regard, the choice of the optimal anesthesia protocol is an important point of research, since an inadequate depth of anesthesia or the influence of undesirable factors can lead to death; the type, duration, and goals of the procedure should be also taken into account. We have aimed to find out what has changed in anesthesia of laboratory animals lately, which drugs are currently relevant and what is the reason for their popularity. Anesthesia of mice is challenging for several reasons: animal size, metabolic rate, and high risk of hypothermia and hypoglycemia. In addition, anesthetics affect physiological parameters and therefore even more affect the results of experiments. At the moment, there is a large list of drugs used in laboratory animals. Since they are divided into groups depending on the routes of administration, we selected the following drugs from a number of articles: injectable anesthetics (medetomidine, dexmedetomidine, zoletil‑100, ketamine, xyla, propofol) and inhalation anesthetics (isoflurane, sevoflurane). Advantages and disadvantages of the drugs and their combinations were studied and described. An analysis of the literature showed that injection anesthesia is considered the main method of anesthesia for experimental animals and is relatively well tolerated by animals; it also does not require additional bulky equipment and additional staff qualifications, there are antagonists for a number of drugs, and is also affordable. In the majority of studies inhalation anesthesia was used in long-term complex manipulations/operations, since it is more manageable, agents require minimal metabolism, and in some cases do not require additional sedation.

Melatonin attenuates spatial learning and memory dysfunction in developing rats by suppressing isoflurane-induced endoplasmic reticulum stress via the SIRT1/Mfn2/PERK signaling pathway

Use of the inhalation anesthetic isoflurane may increase the risk of cognitive deficiency and neurotoxicity after birth. A growing body of evidence suggests that melatonin is an effective treatment for various types of oxidative stress damage and neurodegenerative disease. In this study, we aimed to examine the effects of melatonin on isoflurane-induced endoplasmic reticulum (ER) stress, spatial learning and memory impairment during development. The rats were grouped according to whether the rats were exposed to isoflurane or a control gas and whether they were administered melatonin or phosphate buffered saline (PBS). We administered isoflurane to 7-day-old Sprague–Dawley rat pups with intraperitoneal injections of melatonin (20 mg/kg) 15 min before and 3 h after the initiation of anesthesia. Twelve hours after isoflurane anesthesia, rats were randomly selected from each group and sacrificed. The hippocampal tissue and serum were collected to determine the levels of SIRT1, Mfn2, PERK, and other proteins or cytokines related to ER stress, apoptosis, and neuroinflammation. Subsequently, all remaining rats were assessed for spatial learning and memory deficiency 31 days after birth using the Morris water maze test. We found that melatonin attenuated isoflurane-induced ER stress and neuroapoptosis in the hippocampus and decreased the level of neuroinflammatory markers in the serum of newborn rats, resulting in improved spatial learning and memory. In addition, the neuroprotective effect of melatonin was weakened after the SIRT1/Mfn2/PERK signaling pathway was suppressed by lentivirus transfection. Therefore, our findings demonstrate that melatonin ameliorates spatial learning and memory impairment after isoflurane exposure, and these beneficial effects are associated with a reduction in ER stress, neuroapoptosis, and neuroinflammation via the SIRT1/Mfn2/PERK signaling pathway.

High anesthetic (isoflurane) indoor pollution is associated with genetic instability, cytotoxicity, and proliferative alterations in professionals working in a veterinary hospital.

This is the first study to monitor anesthetic pollution in veterinary operating rooms (VOR) and assess the toxicological impact of the inhalational anesthetic isoflurane (exposed group) compared to matched volunteers (control group). DNA damage was evaluated in mononuclear cells by the comet assay while genetic instability (including micronucleus-MN), cell proliferation, and cell death markers were assessed by the buccal MN cytome assay. Residual isoflurane concentrations in VOR (air monitoring) lacking the scavenging system were assessed by infrared spectrophotometry; the mean concentration was 11ppm (≥ 5 times above the international recommended threshold). Comet assay results did not differ between groups; however, both younger exposed professionals (with higher week workload) compared to older individuals exposed for the same period and older professionals with greater time of exposure (years) compared to those in the same age group with fewer years of exposure presented higher DNA damage. The exposed group had a higher frequency of MN, nuclear buds, binucleated cells, karyorrhexis, and karyolysis and a lower frequency of basal cells than the control group. Exposed women were more vulnerable to genetic instability and proliferative index; exposed men presented more cytotoxicity. High WAG exposure has deleterious effects on exposed professionals.

Effect of Heptaflourane Inhalation and Anesthesia Induction on Hemodynamics of Elderly Patients Undergoing Elective Gastrointestinal Tumor Surgery

Gastrointestinal stromal tumors (GISTs) are rare malignancies that begin in specific cells in the GI tract's (also known as the digestive tract's) wall. The microenvironment of gastrointestinal cancers has gotten a lot of interest in the last decade. There are various obstacles connected with providing care to individuals with gastrointestinal cancers, especially the elderly. The physiological reserves of elderly individuals are generally depleted, and comorbidities might limit treatment options and increase problems. Surgeons and anesthesiologists must be aware of the measures that must be used while dealing with this fragile population. Anesthesia is a term that refers to the use of drugs to alleviate pain during the surgery and other treatments. Anesthesia is crucial to a patient's successful treatment and recovery. To induce and maintain general anesthesia in the operating room, inhalation anesthetics (isoflurane, halothane, nitrous oxide, sevoflurane, and desflurane, the most commonly used agents in practice today) are utilized. Inhalation anesthetics are drugs used to give general anesthesia for surgery in the operating room. Anesthetics have the potential to cause substantial cardiac depression as well as hemodynamic instability. In this study, we propose the SBWOA (spark bumper whale optimization algorithm), which is used to assess the patient's risk before surgery. The entire experiment was run through Matlab simulations.

Janus Kinase Mediates Faster Recovery From Sevoflurane Anesthesia Than Isoflurane Anesthesia in the Migratory Locusts.

Inhalation anesthetics isoflurane and sevoflurane have been widely used in clinical practice for anesthesia. However, the molecular mechanisms underlying the faster recovery from sevoflurane anesthesia than isoflurane anesthesia remain largely undetermined. Herein, we use RNA-seq, RNA interference, quantitative real-time PCR and western blotting to explore the mechanisms of recovery from isoflurane and sevoflurane anesthesia in the migratory locusts. Although the migratory locusts show similar anesthetic responses to these two chemicals in corresponding half-maximal effective concentrations (EC50s), the recovery from sevoflurane anesthesia is significantly faster than that for isoflurane anesthesia after 30 min of anesthetic exposure. Transcriptome analysis shows that those transcripts involved in cytoskeletal components, Janus kinase (JAK) pathway and cuticle protein are differentially expressed in locust brains in response to isoflurane and sevoflurane. RNAi knockdown confirms that Actin, Myosin-like protein 84B (Mlp84B), JAK and cuticle protein NCP56 do not affect anesthetic response of the locusts to these two chemical anesthetics. Moreover, actin, Mlp84B and NCP56 do not affect differential recovery from isoflurane and sevoflurane anesthesia, whereas RNAi knockdown of JAK and its partner STAT5B does not affect anesthetic recovery from isoflurane but elongates recovery duration from sevoflurane anesthesia. Thus, JAK may mediate faster recovery from sevoflurane anesthesia than from isoflurane anesthesia in the migratory locust. This finding provides novel insights into the molecular mechanism underlying faster recovery from sevoflurane anesthesia than isoflurane anesthesia.

No Difference Among Inhaled Anesthetics on the Growth and Metastasis of Murine 4T1 Breast Cancers in a Mouse Model of Spontaneous Metastasis.

Objective: This study evaluates the effect of the commonly used inhaled anesthetics isoflurane, sevoflurane, and desflurane on the viability and migration of murine 4T1 breast cancer cells, the growth, and lung metastasis in a syngenetic model of spontaneous metastasis. Methods: The murine 4T1 breast cancer cells were exposed to isoflurane (2%), sevoflurane (3.6%), or desflurane (10.3%) for 3 h. Cell viability was measured using the MTT assay. The migratory capacity of 4T1 cells was assessed using a scratch assay after 24 h incubation. Female balb/c mice were subjected to orthotopic implantation of 4T1 cells under anesthesia with one of the inhaled anesthetics: 2% isoflurane, 3.6% sevoflurane, or 10.3% desflurane. Subsequently, resection of primary tumors was performed under the identical anesthetic used during implantation for 3 h. Three weeks later, the mice were euthanized to harvest lungs for ex vivo bioluminescent imaging and histological analysis. Blood was collected for serum cytokine assays by ELISA. Results: There was no difference in cell viability among isoflurane, sevoflurane, desflurane, and control groups (n = 180 for each group, P = 0.648). Sevoflurane but not isoflurane or desflurane significantly increased the migration of 4T1 cells compared to the control group (n = 18, P = 0.024). There was no difference in the growth of the orthotopically implanted primary tumors (n = 12 for the isoflurane group, n = 11 for the sevoflurane group, and for the desflurane group, P = 0.879). Surgical dissection of primary tumors in mice under anesthesia with isoflurane, sevoflurane, or desflurane led to no difference in lung metastasis following surgery (P = 0.789). No significant difference was observed among isoflurane, sevoflurane, and desflurane groups in the serum levels of IL-6 (P = 0.284), CCL-1 (P = 0.591), MCP-1 (P = 0.135), and VEGF (P = 0.354). Conclusion: Our study demonstrated that sevoflurane increased the migration of 4T1 breast cancer cells in vitro. Inhaled anesthetics isoflurane, sevoflurane, and desflurane had no difference on the growth of primary tumor and the lung metastasis of 4T1 cells in the mouse model of spontaneous metastasis with surgical removal of primary tumors.

Laminar distribution of electrically evoked hippocampal short latency ripple activity highlights the importance of the subiculum in vivo in human epilepsy, an intraoperative study

ObjectiveThe goal of this study was to define the pathology and anesthesia dependency of single pulse electrical stimulation (SPES) dependent high-frequency oscillations (HFOs, ripples, fast ripples) in the hippocampal formation. MethodsLaminar profile of electrically evoked short latency (<100 ms) high-frequency oscillations (80−500 Hz) was examined in the hippocampus of therapy-resistant epileptic patients (6 female, 2 male) in vivo, under general anesthesia. ResultsParahippocampal SPES evoked HFOs in all recorded hippocampal subregions (Cornu Ammonis 2−3, dentate gyrus, and subiculum) were not uniform, rather the combination of ripples, fast ripples, sharp transients, and multiple unit activities. Mild and severe hippocampal sclerosis (HS) differed in the probability to evoke fast ripples: it decreased with the severity of sclerosis in CA2−3 but increased in the subiculum. Modulation in the ripple spectrum was observed only in the subiculum with increased fast HFO rate and frequency in severe HS. Inhalational anesthetics (isoflurane) suppressed the chance to evoke HFOs compared to propofol. ConclusionThe presence of early HFOs in the dentate gyrus and early fast HFOs (>250 Hz) in the other subregions indicate the pathological nature of these evoked oscillations. Subiculum was found to be active producing HFOs in parallel with the cell loss in the hippocampus proper, which emphasize the role of this region in the generation of epileptic activity.

Short or moderate-time exposure to the inhalational anesthetics isoflurane and sevoflurane does not alter the marble-burying behavior in mice

Several studies suggest the involvement of glutamatergic neurotransmission in obsessive-compulsive disorder (OCD). Some NMDA glutamatergic receptor antagonists, such as the general anesthetic ketamine, have shown anti-OCD effects in preclinical and clinical studies. Therefore, we investigated whether the inhalational anesthetics isoflurane and sevoflurane, which are general anesthetics acting as NMDA receptor antagonists, would induce the same effects. To test our hypothesis, adult male Swiss mice were exposed to different concentrations of isoflurane (0.5, 1.5 or 3 %) or sevoflurane (0.8, 2.5 or 4 %) for 20 min (short-time exposure) or 1 h (moderate-time exposure) and submitted to the open field test (OFT) and the marble-burying test (MBT) in the same day (acute effect) or 7 days (long-lasting effect) after anesthetics administration. We found that single short or moderate-time exposure to isoflurane or sevoflurane, at sub-anesthetic or anesthetic concentrations, did not affect marble-burying behavior acutely or even 7 days after their administration. The same treatment schedules with isoflurane or sevoflurane did not impair total distance travelled in the OFT. A single moderate-time exposure to isoflurane (3 %) reduced, acutely, the central exploration of the open field, suggesting an anxiogenic-like effect of isoflurane in mice. Our results suggest that isoflurane and sevoflurane may not be promising anti-compulsive drugs.

Adsorption of the inhalation anaesthetic isoflurane by activated carbon fibres with reference data on non-porous carbon

Activated carbon fibres with a range of pore sizes, prepared from pre-oxidized acrylic fibre by physical activation in CO2 at different temperatures and times, were investigated as adsorbents for the inhalation anaesthetic isoflurane (2-chloro-2-(difluoromethoxy)-1,1,1-trifluoroethane). Adsorption–desorption isotherms of isoflurane were determined at 293 K and were analysed by the αS method using reference adsorption data, determined also at 293 K, on non-porous carbon. One of the samples obtained showed a much higher adsorption uptake at 100 mbar than reported in previous studies on different materials, while another sample not only showed a higher adsorption uptake than reported previously, but also a higher adsorption uptake at a pressure as low as 1 mbar showing potential for the capture of isoflurane. The results indicate that isoflurane does not adsorb in fine ultramicropores, of width less than about 0.5 nm. Comparison of the pore size distributions of these materials indicated that the presence of supermicropores, as well as ultramicropores, is relevant for the adsorption of isoflurane even at trace levels. Reference adsorption data for isoflurane on non-porous carbon is also presented.

Sensitivity of inhalation anesthetics isoflurane and sevoflurane for the drug-induced QT-interval prolongation in guinea pigs

We investigated effects of isoflurane and sevoflurane on sparfloxacin-induced QT-interval prolongation in guinea pigs under the monitoring of electrocardiogram and monophasic action potential (MAP), which was compared with those of halothane or non-inhaled anesthetics ketamine/xylazine. Intravenous administration of sparfloxacin at 3 and 10 mg/kg prolonged the QT interval and MAP duration together with bradycardic action under 4 different anesthetic conditions. The order of extent of prolongation of corrected QT interval after the administration of sparfloxacin was isoflurane ≈ sevoflurane ≈ halothane >> ketamine/xylazine, whereas that of the MAP90 at a pacing cycle length of 300 ms was halothane ≥ isoflurane ≈ sevoflurane >> ketamine/xylazine. These results suggest that isoflurane and sevoflurane as well as halothane could sensitize the heart to sparfloxacin-induced QT interval prolongation in guinea pigs.

Adsorption of the Inhalation Anesthetic Isoflurane from Dry and Humid Atmosphere

AbstractFor environmental and occupational safety reasons, the inhalation anesthetic isoflurane must be removed from indoor air in hospitals. The present work investigated experimentally the coadsorption of isoflurane and water on four different commercial adsorbents: two activated carbons and two zeolites. Adsorption isotherms from dry and humid atmosphere are shown and discussed, i.e., mixture data are compared with those of the pure substances. For all four adsorbents the dominant parameter regarding structural properties is the pore size distribution. In the case of the zeolites, the surface chemistry, especially the aluminum content, plays a role, too.

Cytosolic HMGB1 Mediates Autophagy Activation in an Emulsified Isoflurane Anesthesia Cell Model.

Inhalation anesthetic isoflurane may cause an increased risk of cognitive impairment. Previous studies have indicated that this cognitive decline is associated with neuroinflammation mediated by high mobility group box 1 (HMGB1). HMGB1 is released from cells and acts as a damage-associated molecule in neurodegenerative diseases. However, the effect of intracellular HMGB1 during emulsified isoflurane (EI) exposure is poorly understood. The purpose of this study was to investigate the effect of autophagy on neuroprotection, evaluate variation of HMGB1, and determine its role in autophagic flux after EI exposure in vitro. We observed that EI decreased cell viability in a concentration-dependent manner, accompanied by an increase in autophagic flux. EI exposure also elevates the HMGB1 level in cytoplasm. Further, cytosolic HMGB1 was necessary for autophagy by perturbing the beclin1-Bcl-2 interaction. Most importantly, autophagy induction by rapamycin alleviated EI-provoked cell injury, and HMGB1 knockdown induced autophagy inhibition, which exacerbated cell damage. Based on these findings, we propose that autophagic flux is sustained and upregulated in response to EI exposure by increased cytosolic HMGB1, and that autophagy activation serves as a protective mechanism against EI-induced cytotoxicity. Thus, the complex roles of HMGB1 make it pivotal in reducing EI-induced neuronal damage.

Food and Drug Administration Warning on Anesthesia and Brain Development: Implications for Obstetric and Fetal Surgery

(Am J Obstet Gynecol. 2018;218(1):98–102) The United States Food and Drug Administration has warned against the use of general anesthetics and sedation medications for &gt;3 hours in pregnant women in the third trimester and children younger than 3 years old. The anesthetics agents listed included midazolam, propofol, and inhalational anesthetics (isoflurane, sevoflurane, and desflurane). They claim these agents may affect the development of children’s brains.

Abstract P-534: INHALATIONAL VOLATILE ANESTHETIC IN SUPER REFRACTORY STATUS EPILEPTICUS - A CASE SERIES FROM A TERTIARY CARE CENTER

Aims & Objectives: Background:Super Refractory Status Epilepticus (SRSE) is a neurological emergency with significant morbidity and mortality with multiple treatment modalities with variable outcomes and scarce evidence. Aims: We share our experience of using Isoflurane in the management of six children with SRSE between April 2015 to December 2017. Methods Retrospective review of case records during the study period Results From April 2015 to December 2017 there were 13 children who had SRSE out of which, six patients (three male and three female) received continuous Inhalation Anesthetic (Isoflurane). Isoflurane was initiated between 2- 18 days (Mean: 13 days) after failure of continuous midazolam, Thiopentone and Ketamine infusion. All the six children achieved burst suppression within few minutes of initiating isoflurane and it ameliorated both clinical and electrographic seizures. All these children received an average of eight to ten Anti-epileptics (Mean: 9) prior to the initiation of Isoflurane. There was recurrence of seizures in all of them once isoflurane was stopped.Mean Minimum Alveolar Concentration where burst suppression was achieved was 1.1 MAC (0.9 -1.8) and the mean vasotrope inotropic score during therapy was 23 (11- 45) and before therapy was 8(3–30) Complications noted were hypotension (6/6). Two children died and four children survived and in two of them Glasgow outcome score was 2 and other two had 3 at the end of three months. Conclusions Isoflurane was found to be the most effective and consistent drug for intractable seizures in SRSE and it was safe to use.