The use of soapy water and freezing as secondary steps for euthanasia in cave (Blaberus giganteus) and Madagascar hissing (Gromphadorhina portentosa) cockroaches.

OBJECTIVE: To evaluate methods for euthanizing cave cockroaches (CCs; Blaberus giganteus) and Madagascar hissing cockroaches (MHCs; Gromphadorhina portentosa). It was hypothesized that both suggested methods would be effective for humane mass euthanasia of both species. SAMPLE: Approximately 800 CC. METHODS: The CCs were separated into replicate groups of 25, 50, 75, 100, and 150 grams and placed into 3.8-L plastic bags. Twenty-seven MHCs were divided into groups of 2 to 3. The study took place from January to March 2023. All CC groups were exposed to 100% carbon dioxide (CO2) at a rate of 4 L/min until the bag was full. Madagascar hissing cockroaches were similarly anesthetized using either CO2 or 2 mL of isoflurane on a cotton ball in a 1-L container or a combination of CO2 and isoflurane. Once cockroaches were immobile, secondary euthanasia steps were performed. One bag of CCs per weight category was exposed to soapy water (5% Dawn dishwashing liquid), and the second was placed into a -80 °C freezer. The containers of MHCs were evenly exposed to the 2 euthanasia methods. Individuals remained in their secondary euthanasia method for 30 minutes. RESULTS: Regardless of the weight of the CCs within each bag, there was no impact on time (1.8 ± 0.4 minutes [mean ± SD]) to immobility. The failure rates for both species were 0.2% CI (-0.1% to 1.5% [1/413]) for soapy water and 0.5% CI (0.005% to 1.9% [2/414]) for the freezer method. These results support the use of both 2-step euthanasia methods in CCs and MHCs. CLINICAL RELEVANCE: These methods will serve as an evidence-based alternative for humane mass euthanasia in cockroaches.

Isoflurane increases the activity of the vascular matrix metalloproteinase-2 in non-pregnant rats and increases the nitric oxide metabolites in pregnancy.

Surgeries that require general anesthesia occur in 1.5-2% of gestations. Isoflurane is frequently used because of its lower possibility of affecting fetal growth. Therefore, we examined the isoflurane anesthesia-induced effects on maternal hemodynamic and vascular changes. We hypothesized that isoflurane would enhance endothelium-dependent vasodilation as a consequence of increased nitric oxide and decreased metalloproteinases (MMPs). Female rats (n=28) were randomized into 4 groups (7 rats/group): conscious (non-anesthetized) non-pregnant group, non-pregnant anesthetized group, conscious pregnant group, and pregnant anesthetized group. Anesthesia was performed on the 20th pregnancy day, and hemodynamic parameters were monitored. Nitric oxide metabolites, gelatinolytic activity of MMP-2 and MMP-9, and the vascular function were assessed. Isoflurane caused no significant hemodynamic changes in pregnant compared with non-pregnant anesthetized group. Impaired acetylcholine-induced relaxations were observed only in conscious non-pregnant group (by approximately 62%) versus 81% for other groups. Phenylephrine-induced contractions were greater in endothelium-removed aorta segments of both pregnant groups (with or without isoflurane) compared with non-pregnant groups. Higher nitric oxide metabolites were observed in anesthetized pregnant in comparison with the other groups. Reductions in the 75 kDa activity and concomitant increases in 64 kDa MMP-2 isoforms were observed in aortas of pregnant anesthetized (or not) groups compared with conscious non-pregnant group. Isoflurane anesthesia shows stable effects on hemodynamic parameters and normal MMP-2 activation in pregnancy. Furthermore, there were increases in nitric oxide bioavailability, suggesting that isoflurane provides protective actions to the endothelium in pregnancy.

Comparison Between the Protective Effect of Isoflurane and Propofol on Myocardium During Coronary Artery Bypass Grafting: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

OBJECTIVE: Intravenous non-volatile anaesthetics like propofol are commonly used in cardiac surgeries across several countries. Volatile anaesthetics like isoflurane may help in protecting the myocardium and minimize ischaemia-reperfusion injury. Hence, we did this review to compare the cardioprotective effect of isoflurane and propofol among patients undergoing coronary artery bypass grafting (CABG). METHODS: We conducted a search in the databases Medical Literature Analysis and Retrieval System Online (or MEDLINE), Embase, PubMed Central®, ScienceDirect, Google Scholar, and Cochrane Library from inception until April 2021. We carried out a meta-analysis with random-effects model and reported pooled risk ratio (RR) or standardized mean difference (SMD) with 95% confidence interval (CI) depending on the type of outcome. RESULTS: We analysed 13 studies including 808 participants. Almost all were low-quality studies. For cardiac index, the pooled SMD was 0.14 (95% CI: -0.22 to 0.50); for cardiac troponin I, pooled SMD was 0.10 (95% CI: -0.28 to 0.48). For mortality, the RR was 3.00 (95% CI: 0.32 to 28.43); for MI, pooled RR was 1.58 (95% CI: 0.59 to 4.20); and for inotropic drug use, pooled RR was 1.04 (95% CI: 0.90 to 1.21). For length of intensive care unit stay, the pooled SMD was 0.13 (95% CI: -0.29 to 0.55), while pooled SMD for mechanical ventilation time was -0.02 (95% CI: -0.54 to 0.51). CONCLUSION: Isoflurane did not have significant cardioprotective effect compared to propofol following CABG. Hence, the anaesthetists need to check some viable alternatives to manage these patients and reduce the rate of postoperative complications.

Comparison between inhalational anesthetics in terms of DNA damage and immunological markers.

This study compared genetic damage and immunological markers between surgical patients who underwent inhalational anesthesia with isoflurane or sevoflurane. Blood samples were collected from surgical patients (n = 18 in the isoflurane group and n = 17 in the sevoflurane group) at baseline (before the anesthesia procedure) and the day after anesthesia. DNA damage was detected using an alkaline comet assay; proinflammatory interleukin (IL)-6 was detected by flow cytometry, and white blood cells were detected via an automatic hematology analyzer. The characteristics of both groups were similar, and neither of the two anesthetics induced DNA damage. Similarly, mild neutrophilia was observed after anesthesia in both groups. Increased IL-6 levels were observed 1 day after anesthesia regardless of the type of anesthetic, but this increase was greater in the isoflurane group. Our study suggested that isoflurane and sevoflurane administration may contribute to changes in the immune parameters measured, though no genotoxic hazard was identified, in healthy adult patients who undergo low-stress surgery.

Xenobiotics Triggering Acute Intermittent Porphyria and Their Effect on Mouse Brain Respiratory Complexes.

Heme enzyme dysfunction causes a group of diseases called porphyrias. Particularly, a decrease in porphobilinogen deaminase, involved in the third step of heme biosynthesis, leads to acute intermittent porphyria (AIP). Considering our previous works demonstrating the multiplicity of brain metabolisms affected by porphyrinogenic agents, this study aimed to elucidate whether they cause any alteration on the mitochondrial respiratory chain. The activities of respiratory chain complexes (I to IV) were measured in encephalon mitochondria of CF1 male mice receiving volatile anesthetics: isoflurane (2 mL/kg) and sevoflurane (1.5 mL/kg), ethanol (30%), allylisopropylacetamide (AIA) (350 mg/kg), and barbital (167 mg/kg). Moreover, they were compared versus animals with pathological levels of 5-aminolevulinic acid (ALA, 40 mg/kg). Complex I-III activity was induced by isoflurane and decreased by AIA, ethanol, and ALA. Complex II-III activity was increased by sevoflurane and decreased by isoflurane and AIA. Complex II activity was increased by sevoflurane and barbital and decreased by AIA, ethanol, and ALA. Complex IV activity was increased by barbital and ALA and decreased by sevoflurane. The damage to the respiratory chain by ALA could be reflecting the pathophysiological condition of patients with AIP. Better understanding the broad effect of porphyrinogenic drugs and the mechanisms acting on the onset of AIP is vital in translational medicine.

Comparison Between the Protective Effect of Isoflurane and Propofol on Myocardium During Coronary Artery Bypass Grafting: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

ABSTRACT Objective: Intravenous non-volatile anaesthetics like propofol are commonly used in cardiac surgeries across several countries. Volatile anaesthetics like isoflurane may help in protecting the myocardium and minimize ischaemia-reperfusion injury. Hence, we did this review to compare the cardioprotective effect of isoflurane and propofol among patients undergoing coronary artery bypass grafting (CABG). Methods: We conducted a search in the databases Medical Literature Analysis and Retrieval System Online (or MEDLINE), Embase, PubMed Central®, ScienceDirect, Google Scholar, and Cochrane Library from inception until April 2021. We carried out a meta-analysis with random-effects model and reported pooled risk ratio (RR) or standardized mean difference (SMD) with 95% confidence interval (CI) depending on the type of outcome. Results: We analysed 13 studies including 808 participants. Almost all were low-quality studies. For cardiac index, the pooled SMD was 0.14 (95% CI: -0.22 to 0.50); for cardiac troponin I, pooled SMD was 0.10 (95% CI: -0.28 to 0.48). For mortality, the RR was 3.00 (95% CI: 0.32 to 28.43); for MI, pooled RR was 1.58 (95% CI: 0.59 to 4.20); and for inotropic drug use, pooled RR was 1.04 (95% CI: 0.90 to 1.21). For length of intensive care unit stay, the pooled SMD was 0.13 (95% CI: -0.29 to 0.55), while pooled SMD for mechanical ventilation time was -0.02 (95% CI: -0.54 to 0.51). Conclusion: Isoflurane did not have significant cardioprotective effect compared to propofol following CABG. Hence, the anaesthetists need to check some viable alternatives to manage these patients and reduce the rate of postoperative complications.

Rat Grimace Scale as a Method to Evaluate Animal Welfare, Nociception, and Quality of the Euthanasia Method of Wistar Rats.

Refinement of experimental procedures in animal research has the objective of preventing and minimizing pain/distress in animals, including the euthanasia period. This study aimed to evaluate pain associated with six methods of euthanasia in Wistar rats (injectable, inhalational, and physical), by applying the Rat Grimace Scale (RGS), comparing the scores, and determining the method with the highest score that might indicate pain for laboratory rodents. Sixty adult male and female Wistar rats were used and assigned to six treatments: pentobarbital, CO2, decapitation, isoflurane, ketamine + xylazine, and ketamine + CO2. Video recording to assess the RGS scores was performed in four events: basal: 24 h before the procedure; Ti1: three minutes before the procedure; Ti2: during the application of the euthanasia method; and Ti3: immediately after the application until LORR. The main findings of this study showed that, during Ti2, decapitation and ketamine + xylazine had the highest scores (0.6 ± 0.26 and 0.6 ± 0.16, respectively) (p < 0.0001), while at Ti3, CO2 (0.9 ± 0.18) and isoflurane (1.2 ± 0.20) recorded the highest scores (p < 0.0001). According to the present results, decapitation and ketamine + xylazine elicited short-term acute pain, possibly due to tissue damage caused by both methods (injection and guillotine). In contrast, isoflurane's RGS scores recorded during Ti3 might be associated with nociception/pain due to the pungency of the drug or to the pharmacological muscle relaxant effect of isoflurane. Further research is needed to establish a comprehensive study of pain during euthanasia, where RGS could be used minding the limitations that anesthetics might have on facial expression.

A comparison of intra and postoperative analgesic effects of sacrococcygeal and lumbosacral epidural levobupivacaine in cats undergoing ovariohysterectomy.

The aim of this study was to compare the intra and postoperative analgesic effects of sacrococcygeal epidural levobupivacaine with those of lumbosacral levobupivacaine in feline ovariohysterectomy. Thirty-six cats were premedicated with intramuscular acepromazine (0.05 mg/kg) and meperidine (6 mg/kg). Anesthesia was induced with intravenous propofol and maintained with isoflurane in oxygen. The cats were randomly assigned one of the three treatments receiving 0.33% levobupivacaine (0.3 mL/kg) into the sacrococcygeal (S-C group, n=12) or lumbosacral (L-S group, n=12) epidural space, or the same volume of 0.9% saline solution into one of the epidural approaches (Control group, n=12). Intraoperatively, cardiorespiratory variables, end-tidal isoflurane concentration (FE´ISO), and fentanyl requirements were recorded. Postoperative pain was assessed by the UNESP (Universidade Estadual Paulista)-Botucatu multidimensional composite pain scale and the Glasgow feline composite measure pain scale up to 8 hr post-extubation. Morphine was administered as rescue analgesia. Overall FE´ISO and fentanyl requirements were lower in the L-S and S-C compared to the Control (P=0.002-0.048, respectively). There was no significant difference in the cardiorespiratory variables during anesthesia, postoperative pain and rescue analgesia among groups. The time to standing after anesthesia was prolonged in the L-S and S-C groups than in the Control (P<0.001). Lumbosacral and sacrococcygeal epidural levobupivacaine resulted in similar decreases in isoflurane requirements and intraoperative fentanyl supplementation in the cats, with no postoperative benefits.

Thermal Response of Laboratory Rats (Rattus norvegicus) during the Application of Six Methods of Euthanasia Assessed by Infrared Thermography.

Refinement is one of the principles aiming to promote welfare in research animals. The techniques used during an experimental protocol, including euthanasia selection, must prevent and minimize suffering. Although the current euthanasia methods applied to laboratory rodents are accepted, the controversial findings regarding the potential stress/distress they can cause is a field of research. The objective was to assess the thermal response of Wistar rats during various euthanasia methods using infrared thermography (IRT) to determine the method that prevents or diminishes the stress response and prolonged suffering. Pentobarbital (G1), CO2 (G2), decapitation (G3), isoflurane (G4), ketamine + xylazine (G5), and ketamine + CO2 (G6) were evaluated at five evaluation times with IRT to identify changes in the surface temperature of four anatomical regions: ocular (T°ocu), auricular (T°ear), interscapular (T°dor), and caudal (T°tai). Significant differences (p < 0.05) were found in G2 and G4, registering temperature increases from the administration of the drug to the cessation of respiratory rate and heart rate. Particularly, isoflurane showed a marked thermal response in T°ocu, T°ear, T°dor, and T°tai, suggesting that, in general, inhalant euthanasia methods induce stress in rats and that isoflurane might potentially cause distress, an effect that must be considered when deciding humane euthanasia methods in laboratory rodents.

Pregnancy hypertension-associated endothelial dysfunction is attenuated by isoflurane anesthesia: Evidence of protective effect related to increases in nitric oxide.

AIMS: Pregnancy hypertension-induced endothelial dysfunction associated with impairment of nitric oxide (NO) bioavailability and hemodynamic derangements is a challenging for urgent procedures requiring maternal anesthesia. The volatile anesthetic isoflurane has demonstrated NO-associated protective effects. However, this isoflurane-induced effect is still unclear in pregnancy hypertension. Therefore, the present study examined the potential protective effects of isoflurane anesthesia on endothelial dysfunction and hemodynamic changes induced by hypertensive pregnancy associated with fetal and placental growth restrictions. MATERIALS AND METHODS: Animals were distributed into four groups: normotensive pregnant rats (Preg), anesthetized pregnant rats (Preg+Iso), hypertensive pregnant rats (HTN-Preg), and anesthetized hypertensive pregnant rats (HTN-Preg+Iso). Systolic and diastolic pressures, mean arterial pressure (MAP), heart rate, fetal and placental weights, vascular contraction, endothelium-derived NO-dependent vasodilation, and NO levels were assessed. The vascular endothelial growth factor (VEGF) levels and endothelial NO synthase (eNOS) Serine (1177) phosphorylation (p-eNOS) expression were also examined. KEY FINDINGS: Isoflurane produced more expressive hypotensive effects in the HTN-Preg+Iso versus Preg+Iso group, with respective reductions in MAP by 50 ± 13 versus 25 ± 4 mmHg (P < 0.05). Also, HTN-Preg+Iso compared to the HTN-Preg group showed (respectively) preventions against the weight loss of the fetuses (4.0 ± 0.6 versus 2.8 ± 0.6 g, P < 0.05) and placentas (0.37 ± 0.06 versus 0.30 ± 0.06 mg, P < 0.05), hyper-reactive vasocontraction response (1.8 ± 0.4 versus 2.8 ± 0.6 g, P < 0.05), impaired endothelium-derived NO-dependent vasodilation (84 ± 8 versus 50 ± 17 %, P < 0.05), reduced VEGF levels (147 ± 46 versus 25 ± 13 pg/mL, P < 0.05), and decreased p-eNOS expression (0.24 ± 0.07 versus 0.09 ± 0.05 arbitrary units, P < 0.05). SIGNIFICANCE: Isoflurane anesthesia protects maternal endothelial function in pregnancy hypertension, and possibly endothelium-derived NO is involved.

Repeated Administration of the Cannabinoid WIN Alters the Isoflurane-Sparing Effect of Morphine and Dexmedetomidine.

The impacts of morphine and dexmedetomidine on the MAC of isoflurane were studied in rats constantly medicated with the cannabinoid WIN 55,212-2. METHODS: Prior to the administration of morphine, the MAC was measured in both untreated rats (MAC (ISO)) and those treated with a cannabinoid (MAC (ISO + CANN)). The effects of morphine (MAC (ISO + MOR)) and dexmedetomidine (MAC (ISO + DEX)) on untreated rats and rats treated for 21 days with the cannabinoids (MAC (ISO + CANN + MOR)) and (MAC (ISO + CANN + DEX) were also studied. RESULTS: MAC (ISO) was 1.32 ± 0.06, and MAC (ISO + CANN) was 1.69 ± 0.09. MAC (ISO + MOR) was 0.97 ± 0.02 (26% less than MAC (ISO)). MAC (ISO + CANN + MOR) was 1.55 ± 0.08 (8% less than MAC (ISO + CANN)), MAC (ISO + DEX) was 0.68 ± 0.10 (48% less than MAC (ISO)), and MAC (ISO + CANN + DEX) was 0.67 ± 0.08 (60% less than MAC (ISO + CANN)). CONCLUSIONS: Medication with a cannabinoid for 21 days augmented the MAC of isoflurane. The sparing effect of morphine on isoflurane is lower in rats constantly medicated with a cannabinoid. The sparing effect of dexmedetomidine on the minimum alveolar concentration of isoflurane is greater in rats repeatedly medicated with a cannabinoid.

Neobaicalein prevents isoflurane anesthesia-induced cognitive impairment in neonatal mice via regulating CREB1.

OBJECTIVES: Isoflurane (ISO) is widely used in the clinic and research. The authors aimed to explore whether Neobaicalein (Neob) could protect neonatal mice from ISO-induced cognitive damage. METHOD: The open field test, Morris water maze test, and tail suspension test was performed to assess the cognitive function in mice. Enzyme-linked immunosorbent assay was used to evaluate inflammatory-related protein concentrations. Immunohistochemistry was used to assess Ionized calcium-Binding Adapter molecule-1 (IBA-1) expression. Hippocampal neuron viability was detected using the Cell Counting Kit-8 assay. Double immunofluorescence staining was employed to confirm the interaction between proteins. Western blotting was used to assess protein expression levels. RESULTS: Neob notably improved cognitive function and exhibited anti-inflammatory effects; moreover, under iso-treatment, it exhibited neuroprotective effects. Furthermore, Neob suppressed interleukin-1ß, tumor necrosis factor-α, and interleukin-6 levels and upregulated interleukin-10 levels in ISO-treated mice. Neob significantly mitigated iso-induced increases in IBA-1-positive cell numbers of the hippocampus in neonatal mice. Furthermore, it inhibited ISO-induced neuronal apoptosis. Mechanistically, Neob was observed to upregulate cAMP Response Element Binding protein (CREB1) phosphorylation and protected hippocampal neurons from ISO-mediated apoptosis. Moreover, it rescued ISO-induced abnormalities of synaptic protein. CONCLUSIONS: Neob prevented ISO anesthesia-induced cognitive impairment by suppressing apoptosis and inflammation through upregulating CREB1.

Sevoflurane and isoflurane anesthesia induce redox imbalance, but only sevoflurane impairs vascular contraction.

Volatile anesthetics may cause vascular dysfunction; however, underlying effects are unclear. The aim of the present study was to investigate whether sevoflurane and isoflurane affect vascular function, nitric oxide (NO) bioavailability, and biomarkers of oxidative stress and inflammation. Wistar rats were divided into three experimental groups: Not anesthetized (control group) or submitted to anesthesia with isoflurane (Iso group) or sevoflurane (Sevo group). Hemodynamic parameters were monitored during anesthesia, and blood gas values and biochemical determinants were analyzed. Isometric contractions were recorded in aortic rings. Vasoconstriction induced by potassium chloride (KCl) and phenylephrine (Phe) were measured. No differences in hemodynamic parameters and blood gasses variables were observed. Impaired KCl and Phe-induced contractions were observed in endothelium-intact aorta of Sevo compared to Iso and Control groups. Redox imbalance was found in Sevo and Iso groups. Reduced NO bioavailability and increased activity of matrix metalloproteinase 2 (MMP-2) were observed in Sevo, but not in the Iso group. While reduced IL-10 and IL-1ß were observed in Sevo, increases in IL-1ß in the Iso group were found. Sevoflurane, but not isoflurane, anesthesia impairs vasocontraction, and reduced NO and cytokines and increased MMP-2 activity may be involved in vascular dysfunction after sevoflurane anesthesia.

Acute exposure to isoflurane impairs sperm parameters in mice.

Isoflurane, an inhalational anesthetic from the halogenated group, has been increasingly used in the medical and scientific fields. Due to its characteristics, it is capable of inducing anesthesia quickly and quietly; however, the adverse effects resulting from its use have not yet been fully elucidated, especially with regard to reproductive aspects. Considering its common use in research laboratories, whether for performing surgical procedures or for prior exposure to euthanasia, knowledge about its interference in sperm parameters of experimental models characterizes an important study goal. The aim of the present study was to determine the interference of acute exposure to isoflurane on the sperm quality of mice, both immediately previous to euthanasia and in later evaluation, twenty days after a single anesthetic exposure. Our results demonstrate that acute anesthetic exposure reduces sperm motility and is responsible for the formation of damaged sperm cells that are prone to apoptosis, which may affect the outcome of reproductive experiments even 20 days after exposure.

Minimización de costos de sedación usando anestesia inhalada. Análisis en la UTI durante la pandemia por COVID-19 / Minimization of sedation costs using inhaled anesthesia. Analysis in the ICU during the COVID-19 pandemic / Minimização dos custos de sedação usando anestesia inalatória. Análise na UTI durante a pandemia de COVID-19

Resumen: Introducción: los sedantes de uso no convencional y aquéllos fuera de recomendación como los anestésicos inhalados se usaron ante la escasez de medicamentos durante la pandemia por SARS-CoV-2. Objetivos: comparar el costo y resultados obtenidos con el uso de anestésicos inhalados versus sedantes intravenosos en COVID-19. Material y métodos: estudio retrospectivo en una unidad de terapia intensiva (UTI) de un hospital público de referencia. Se hizo un cálculo de costos de sedación de los dos primeros días de estancia en la UTI. Las dosis de fármacos fueron tomadas del expediente clínico y los costos de adquisición directamente de CompraNet. Se comparan medias de costos por medicamento y por grupo. Resultados: de 151 pacientes, 81 recibieron sedación intravenosa y 70 anestesia inhalada con o sin sedantes intravenosos. No hubo diferencia en mortalidad, días de ventilación mecánica, estancia en la UTI y estancia hospitalaria entre grupos. Se observó una reducción significativa de costos derivados del menor uso de midazolam, propofol y dexmedetomidina (p < 0.0001) cuando se usó anestesia inhalada y una diferencia entre medias de costos totales de sedación de $4,108.42 M.N. por día por paciente. Conclusiones: la anestesia inhalada durante la pandemia por COVID-19 permitió una reducción de costos comparada con sedación intravenosa en los primeros dos días de estancia en la UTI.

Abstract: Introduction: non-conventional sedatives and those off-label, such as inhaled anesthetics, were used due to the shortage of medicines during the SARS-CoV-2 pandemic. Objectives: to compare the cost and results obtained with the use of inhaled anesthetics versus intravenous sedatives in COVID-19. Material and methods: retrospective study in a public reference hospital ICU. A calculation of sedation costs was made of the first two days of ICU stay. Drug doses were taken from the clinical records and acquisition costs directly from CompraNet. Mean costs per medication and per group are compared. Results: of 151 patients, 81 received intravenous sedation and 70 received inhaled anesthesia with or without intravenous sedatives. There was no difference in mortality, days of mechanical ventilation, ICU stay, and hospital stay between groups. A significant reduction in costs derived from the less use of midazolam, propofol and dexmedetomidine (p < 0.0001), and a difference between means of total sedation costs of $4,108.42 Mexican pesos per patient per day was observed with inhaled anesthesia. Conclusions: inhaled anesthesia during the COVID-19 pandemic compared to intravenous sedation allowed a cost reduction in the first two days of ICU stay.

Resumo: Introdução: sedativos de uso não convencional e não recomendados, como anestésicos inalatórios, foram utilizados devido à escassez de medicamentos durante a pandemia de SARS-CoV-2. Objetivos: comparar o custo e os resultados obtidos com o uso de anestésicos inalatórios versus sedativos intravenosos na COVID-19. Material e métodos: estudo retrospectivo em uma UTI de um hospital público de referência. Foi feito um cálculo dos custos de sedação para os dois primeiros dias de internação na UTI. As doses dos medicamentos foram retiradas do prontuário clínico e os custos de aquisição diretamente do CompraNet. Os custos médios por medicamento e por grupo são comparados. Resultados: dos 151 pacientes, 81 receberam sedação intravenosa e 70 anestesia inalatória com ou sem sedativos intravenosos. Não houve diferença na mortalidade, dias em ventilação mecânica, permanência na UTI e internação entre os grupos. Uma redução significativa nos custos derivados do menor uso de midazolam, propofol e dexmedetomidina (p < 0.0001) foi observada quando a anestesia inalatória foi usada e uma diferença entre as médias dos custos totais de sedação de $4,108.42 M.N. por dia por paciente. Conclusões: a anestesia inalatória durante a pandemia de COVID-19 permitiu redução de custos em comparação com a sedação endovenosa nos primeiros dois dias de internação na UTI.

Neuroprotective potential of sevoflurane against isoflurane induced cognitive dysfunction in rats via anti-inflammatory and antioxidant effect

Purpose: Intravenous anesthetics have excellent analgesic activity without inducing the side effect in the respiratory system. The aim and objective of the current experimental study was to access the neuroprotective effect of sevoflurane against isoflurane induced cognitive dysfunction in rats. Methods: Isoflurane was used for induction the neurodysfunction in the rats, and rats received the oral administration of sevoflurane (2.5, 5 and 10 mg/kg). Morris water test was carried out for the estimation of cognitive function. Neurochemical parameters, antioxidant parameters and pro-inflammatory cytokines were also estimated. Results: Sevoflurane significantly (P < 0.001) altered the neurochemical parameters such as anti-choline acetyltransferase, acetylcholine esterase, acetylcholine, protein carbonyl, choline brain-derived neurotrophic factor, and amyloid ß; antioxidant parameters such as glutathione, superoxide dismutase, and malondialdehyde; pro-inflammatory cytokines include interleukin (IL-2, IL-10, IL-4, IL-6, IL-10, IL-1ß), and tumor necrosis factor-α. Sevoflurane significantly reduced the activity of caspase-3. Conclusions: Sevoflurane exhibited the neuroprotection against the cognitive dysfunction in rats via anti-inflammatory and antioxidant mechanism.

Neobaicalein prevents isoflurane anesthesia-induced cognitive impairment in neonatal mice via regulating CREB1

Abstract Objectives: Isoflurane (ISO) is widely used in the clinic and research. The authors aimed to explore whether Neobaicalein (Neob) could protect neonatal mice from ISO-induced cognitive damage. Method: The open field test, Morris water maze test, and tail suspension test was performed to assess the cognitive function in mice. Enzyme-linked immunosorbent assay was used to evaluate inflammatory-related protein concentrations. Immunohistochemistry was used to assess Ionized calcium-Binding Adapter molecule-1 (IBA-1) expression. Hippocampal neuron viability was detected using the Cell Counting Kit-8 assay. Double immunofluorescence staining was employed to confirm the interaction between proteins. Western blotting was used to assess protein expression levels. Results: Neob notably improved cognitive function and exhibited anti-inflammatory effects; moreover, under isotreatment, it exhibited neuroprotective effects. Furthermore, Neob suppressed interleukin-1β, tumor necrosis factor-α, and interleukin-6 levels and upregulated interleukin-10 levels in ISO-treated mice. Neob significantly mitigated iso-induced increases in IBA-1 - positive cell numbers of the hippocampus in neonatal mice. Furthermore, it inhibited ISO-induced neuronal apoptosis. Mechanistically, Neob was observed to upregulate cAMP Response Element Binding protein (CREB1) phosphorylation and protected hippocampal neurons from ISO-mediated apoptosis. Moreover, it rescued ISO-induced abnormalities of synaptic protein. Conclusions: Neob prevented ISO anesthesia-induced cognitive impairment by suppressing apoptosis and inflammation through upregulating CREB1.

Minimum Alveolar Concentration of Isoflurane in Rats Chronically Treated with the Synthetic Cannabinoid WIN 55,212-2.

The minimum alveolar concentration MAC of isoflurane was measured in rats chronically treated with WIN 55,212-2. METHODS: The MAC of isoflurane was determined in 24 male rats from expiratory samples at time of tail clamping under the following conditions: without treatment MAC(ISO), in rats treated for 21 days with WIN 55,212-2 MAC(ISO + WIN55), and in rats 8 days after stopping treatment with WIN 55,212-2 (MACISO + WIN55 + 8D). RESULTS: The MAC(ISO) was 1.32 ± 0.06. In the MAC(ISO + WIN55) group, the MAC increased to 1.69 ± 0.09 (28%, p-value ≤ (0.0001). Eight days after stopping treatment with WIN55, the MAC did not decrease significantly, 1.67 ± 0.07 (26%, p-value ≤ 0.0001). CONCLUSIONS: The administration of WIN 55,212-2 for 21 days increases the MAC of isoflurane in rats. This effect does not disappear 8 days after discontinuation of treatment with the synthetic cannabinoid.