Isoflurane Concentration Research Articles

A Comparative Study of Common Anesthetics Propofol, Sevoflurane, Isoflurane and Ketamine on Lipid Membrane Fluidity

The membrane fluidity increases induced by popular anesthetic agents (propofol, isoflurane, sevoflurane, and ketamine/xylazine) were measured at the clinical and supra-clinical concentrations in red blood cell (RBC) membrane as well as four model membranes. Membrane fluidity changes were monitored using the excimer/monomer (E/M) ratio of dipyrene-PC and fluorescence anisotropies of DPH-PC and TMA-DPH. Propofol, sevoflurane and isoflurane increased membrane fluidity instantaneously. The largest increase occurs in membranes made of saturated lipids. RBCs were labeled with TMA-DPH, and the increase in membrane fluidity at clinical concentrations of isoflurane and sevoflurane was more than that induced by ten times the legal limit of alcohol in human blood. However, membrane fluidity was essentially unchanged by ketamine/xylazine up to 210 µM. These results strongly correlate with our recent in vivo experiments and reveal a clear connection between increasing membrane fluidity in model membranes, increasing the blood–brain barrier (BBB) permeability in mice, and inducing effective anesthesia in animals. Interestingly, at the most commonly used clinical concentrations, the membrane fluidity increases induced by propofol, sevoflurane, and isoflurane were very similar, despite the fact that different categories of anesthetics were used and their chemical concentrations were different by 100 times. This indicates that at clinical concentrations of these anesthetics, a similar level of membrane disruption at the BBB is achieved. Thus, our results strongly support the lipid hypothesis of the mechanism of general anesthetics.

An accelerometry-based, low cost and non-invasive respiration monitoring in anesthetized mice

Respiratory rate monitoring is essential especially for anesthetized animals in veterinary and biomedical research. Current methods often rely on invasive or wearable devices, which can stress animals, especially smaller ones like rodents. Here we present a non-invasive, environmentally integrated device that detects subtle breathing movements through waveform analyzed data via a triaxial accelerometer under a flexible fabric sheet in a trampoline-like box. The accuracy of the system was tested on anesthetized mice under varying isoflurane concentrations (1 to 3%) by comparison with a laser displacement sensor. The accelerometer data closely correlated with that from a laser displacement sensor, particularly under deeper anesthesia, with minimal deviations in respiratory rate detection. This method may provide a promising alternative for animal respiratory monitoring.

Mild hypothermia is associated with altered volume kinetic parameters of an intravenous crystalloid fluid bolus in healthy isoflurane-anesthetized cats

Abstract OBJECTIVE To assess the impact of mild hypothermia on the distribution and elimination of an IV crystalloid fluid bolus in healthy anesthetized cats using volume kinetic (VK) analysis. METHODS 10 adult cats were anesthetized and included in a prospective, randomized, cross-over study. The subjects were maintained either normothermic (38.3 ± −16.9 °C) or mildly hypothermic (35 ± −16.9 °C), with a 7-day washout period between anesthetic episodes. All cats received 20 mL/kg of a balanced isotonic solution (Normosol-R) IV over 20 minutes, following the achievement and stabilization of target temperature. Hemoglobin concentration, PCV, and urinary output were measured at established time points and served as input variables for VK analysis. RESULTS Hypothermia was associated with a larger central compartment volume (Vc); higher body weights were associated with an increased Vc and a decreased elimination rate; higher end-tidal isoflurane concentration (ETISO) was associated with an increased Vc and a higher distribution rate constant. Heart rate, blood pressure, and ETISO were significantly lower in the hypothermic group. No statistically significant difference was observed in urinary output between groups. CONCLUSIONS Body weight, temperature, and ETISO were significant covariates affecting VK parameters. Hypothermia did not induce cold diuresis but was associated with an increase in Vc. The negative relationship between body weight and the elimination rate constant requires further verification. Hypothermia was associated with lower heart rate and blood pressure despite reduced ETISO. CLINICAL RELEVANCE Hypothermia was associated with smaller plasma volume expansion from fluid bolus. Fluid dosing based on ideal body weight should be considered to avoid overdosing.

Effects of Progesterone on Isoflurane Requirement for Balance Disturbance and Loss of Righting Reflex in Male Mice.

Introduction It has been known that progesterone has central effects, as measured by minimum alveolar concentration in various experimental settings. Previously, we showed that progesterone reduces the sevoflurane requirement for the loss of righting reflex (LORR) using male mice. However, the combination of progesterone and isoflurane has not been studied. Therefore, in this study, we compared the effect of progesterone on anesthetic requirements in a mouse model. Methods Male C57BL/6 mice were treated with either progesterone (75 mg/kg) + olive oil or only olive oil. Animals were studied in closed cylinders supplied with oxygen and isoflurane that rotated four times per minute. Balance disturbance and loss of the righting reflex were counted. The data were analyzed by using a multiple independent variable logistics regression model. Results The concentrations at the onset of balance disturbances, represented by the effective dose 50% (ED50) and effective dose 95% (ED95) of isoflurane, were 0.37% and 0.45% for the control group and 0.34% and 0.41% for the progesterone group, respectively. Similarly, the concentrations for loss of righting reflex (LORR), represented by ED50 and ED95, were 0.55% and 0.62% for the control group and 0.53% and 0.60% for the progesterone group, respectively. Subcutaneous injection of progesterone at a dose of 75 mg/kg significantly reduced the isoflurane requirement for both balance disturbance (p = 0.0022) and LORR (p = 0.0218). Conclusion We conclude that progesterone decreased isoflurane concentration for both balance disturbance and LORR.

Effect of buprenorphine delivered by target-controlled infusion on the minimum alveolar concentration of isoflurane in cats

ObjectiveTo characterize the effect of buprenorphine on the minimum alveolar concentration of isoflurane (MACiso) in cats. Study designRandomized, crossover, experimental study. AnimalsA group of six healthy male neutered cats, aged 2–8 years with body mass 5.0 ± 0.3 kg. MethodsThe MACiso had been determined in each cat in a previous study. Cats were anesthetized with isoflurane in oxygen. Catheters were placed in a medial saphenous vein for drug and fluid administration and in a jugular vein for blood sampling. Buprenorphine was administered intravenously using a target-controlled infusion system to reach and maintain plasma concentrations of 0.5, 1, 2, 4, 8, 16, 32 and 64 ng mL–1, and MACiso was determined in duplicate at each concentration using the tail clamp technique. Four target plasma buprenorphine concentrations were administered on each study day, with at least 2 weeks between experiments. Blood was sampled after the second MAC determination at each target for determination of plasma buprenorphine concentration. ResultsA significant effect of buprenorphine on MAC was found; however, pairwise comparisons to MACiso without buprenorphine did not reach statistical significance. Maximum reduction in MACiso in individual cats ranged from 2% to 34% at plasma buprenorphine concentrations ranging from 0.25 to 8.15 ng mL–1. Conclusions and clinical relevanceAlthough buprenorphine significantly affected MACiso in cats, the magnitude of the effect and the plasma concentration at which the largest effect occurred was highly variable among cats, limiting the clinical usefulness of buprenorphine as an agent to reduce MAC in cats.

Effect of Propofol and Isoflurane on Hemodynamic changes during Spinal Surgery Under General Anesthesia

Background: Hemodynamic stability are vital requirements of up-to-date anesthesia. Both propofol and isoflurane meet these criteria though the clinical effects like postoperative nausea vomiting after administering propofol and isoflurane have been studied in various surgeries but have not been much evaluated or studied in patients undergoing major surgical procedures like spine surgeries, There’ is definite advantage of one technique over the other. Isoflurane has a low blood gas partition coefficient, which contributes to rapid induction and emergence from anaesthesia than with other volatile anesthetics in current clinical use. Propofol has been established as the intravenous agent that provides faster and smoother recovery & peri operative hemodynamic stability. Objective: To compare the effects of isoflurane and propofol regarding hemodynamic status in spinal surgery under general anaesthesia. Methods: After getting ethical approval, a randomized controlled trial study design was performed where patients were selected in the pre-anesthetic checkup room based on inclusion and exclusion criteria for those who were scheduled for spine surgeries under general anesthesia is admitted in the Department of Neurosurgery in East West Medical College from January 2023 – December 2024. A total number of 40 patients were selected. 20 patients were enrolled each in group A and group B by lottery method in a sealed envelope. They were divided into two groups by randomization; Group A and Group B. A written informed consent was taken from all selected patients. Patients were advised to fast for at least 8 hours before intervention. In Group A, anesthesia is maintained with propofol infusion, nitrous oxide (66%), and oxygen (33%) while in Group B, anesthesia is maintained with Isoflurane, nitrous oxide (66%), and oxygen (33%). All patients were given N2O in oxygen and 1.25% inspired concentration of Isoflurane (MAC -1.15). In Group A propofol infusion at rate of 80 μg/kg/min (fixed from the beginning). All data was collected at –Just after starting, 15 minutes, 30-minute, 1 hour, and >1 hour interval per operatively. Data was compiled, edited and plotted in tabular and figure form. P value was determined as significant when it was <0.05. Results: 40 patients yielded the following results. The mean age of Group A and B were 32.56±12.55 years and 34.6±12.5 years. Mean difference of heart rate was lower in Group A than that of Group B. Other parameters in both groups were confined to good and acceptable categories. But interestingly, there was a statistically significant difference found between Group A and Group B in Systolic Blood Pressure (SBP) & Diastolic Blood Pressure (DBP). The scoring was far better in Group A than Group B. Mean SBP was higher in Group B than Group A (p= >0.05). Similarly, mean DBP was also higher in Group B than Group A (p = >0.05). Conclusion: Propofol is better for maintaining hemodynamic status than Isoflurane for Spine surgery under General anaesthesia. EWMCJ Vol. 12, No. 1&2, January-July 2024: 21-26

Mouse aversion to induction with isoflurane using the drop method.

Isoflurane anesthesia prior to carbon dioxide euthanasia is recognized as a refinement by many guidelines. Facilities lacking access to a vaporizer can use the "drop" method, whereby liquid anesthetic is introduced into an induction chamber. Knowing the least aversive concentration of isoflurane is critical. Previous work has demonstrated that isoflurane administered with the drop method at a concentration of 5% is aversive to mice. Other work has shown that lower concentrations (1.7% to 3.7%) of isoflurane can be used to anesthetize mice with the drop method, but aversion to these concentrations has not been tested. We assessed aversion to these lower isoflurane concentrations administered with the drop method, using a conditioned place aversion (CPA) paradigm. Female C57BL/6J (OT-1) mice (n = 28) were randomly allocated to one of three isoflurane concentrations: 1.7%, 2.7%, and 3.7%. Mice were acclimated to a light-dark apparatus. Prior to and following dark (+ isoflurane) and light chamber conditioning sessions, mice underwent an initial and final preference assessment; the change in the duration spent within the dark chamber between the initial and final preference tests was used to calculate a CPA score. Aversion increased with increasing isoflurane concentration: from 1.7% to 2.7% to 3.7% isoflurane, mean ± SE CPA score decreased from 19.6 ± 20.1 s to -25.6 ± 23.2 s, to -116.9 ± 30.6 s (F1,54 = 15.4, p < 0.001). Our results suggest that, when using the drop method to administer isoflurane, concentrations between 1.7% and 2.7% can be used to minimize female mouse aversion to induction.

Case study: chemical contaimnent in parrots (Amazona SP - Lesson, 1830) from de Quinzinho de Barros Zoological Park, municipality of Sorocaba, São Paulo

The containment and anesthesia of wild animals is extremely important for veterinarians who intend to or already practice in this field. However, before administering anesthesia, it is essential to understand the pharmacology of anesthetics and the biological aspects related to the anatomical, physiological, and behavioral peculiarities of the species to be restrained. The aim of this research was to evaluate parameters such as heart rate (HR), respiratory rate (RR), temperature (T°), muscle relaxation, reflexes (palpebral, ocular, and pedal), and respiratory pattern in four anesthetic protocols: ketamine 5% at a dose of 30mg/kg combined with xylazine 2%-2mg/kg; ketamine 5% at doses of 15mg/kg and 20mg/kg with diazepam 1% at a dose of 1mg/kg; diazepam 0.5% at a dose of 5mg/kg 15 minutes before isoflurane administration; and the use of isoflurane alone in parrots (Amazona sp) kept at the Quinzinho de Barros Municipal Park, Sorocaba, São Paulo. Eleven animals were used: three with the ketamine combined with xylazine protocol, three with ketamine plus diazepam, three with diazepam before isoflurane, and two with the isolated use of isoflurane. The results of this research showed that with the use of ketamine combined with xylazine at this dosage, only superficial sedation was achieved. With the supplementary dose of ketamine and xylazine, the animal reached a moderate anesthetic plane, but respiratory depression occurred. The use of diazepam combined with ketamine 5% at a dose of 15mg/kg is only recommended for minor procedures. Recovery was slightly less prolonged and with less cardiorespiratory depression compared to the use of ketamine combined with xylazine. Diazepam 0.5%-5mg/kg before isoflurane did not allow for the intubation of the animal; it served to reduce the stress of restraint, requiring a lower concentration of isoflurane for induction. Apnea was observed with the increase of isoflurane concentration, even with the use of diazepam before isoflurane. With the isolated use of isoflurane, the animal reached a moderate to deep anesthetic plane, which would allow for more invasive procedures.

Role of pterygopalatine ganglion in regulating isoflurane-induced cerebral hyper-perfusion

Cerebral perfusion is functionally regulated by neural mechanisms in addition to the systemic hemodynamic variation, vascular reactivity and cerebral metabolism. Although anesthesia is generally esteemed to suppress the overall brain neural activity and metabolism, a few inhalation anesthetics, such as isoflurane, can increase cerebral perfusion, thus heightening the risks of higher intracranial pressure, bleeding, and brain edema during surgery. With the aid of laser speckle contrast imaging, we observed a transient yet limited effect of cerebral perfusion enhancement in mice from awake to anesthetized conditions with different concentration of isoflurane. Retrograde and antegrade tracing revealed a higher proportion of parasympathetic control more than sympathetic innervation for the blood vessels. Surprisingly, isoflurane directly activated pterygopalatine ganglion (PPG) explants and induced FOS expression in the cholinergic neurons. Chemogenetic activation of cholinergic PPG neurons reduced isoflurane-related cerebral perfusion. On the contrary, ablation of the cholinergic PPG neurons resulted in further enhancement of cerebral perfusion induced by isoflurane. While blocking muscarinic cholinergic receptors resulted in the overall reduction upon isoflurane stimulation, the blockage of nicotinic cholinergic receptors enhanced the isoflurane-induced cerebral perfusion only when PPG neurons exist. Collectively, these results suggest that PPG play important roles in regulating cerebral perfusion under isoflurane inhalation.

An anesthetic protocol for preserving functional network structure in the marmoset monkey brain

Abstract Initiatives towards acquiring large-scale neuroimaging data in non-human primates promise improving translational neuroscience and cross-species comparisons. Crucial among these efforts is the need to expand sample sizes while reducing the impact of anesthesia on the functional properties of brain networks. Yet, the effects of anesthesia on non-human primate brain networks remain unclear. Here, we demonstrate using functional magnetic resonance imaging (fMRI) at 9.4 tesla that isoflurane anesthesia induces a variety of brain states in the marmoset brain with dramatically altered functional connectivity profiles. As an alternative, we recommend using a continuous infusion of the sedative medetomidine, supplemented with a low concentration of isoflurane. Using this protocol in eight marmosets, we observed robust visual activation during flickering light stimulation and identified resting-state networks similar to the awake state. In contrast, isoflurane alone led to a suppressed visual activation and the absence of awake-like network patterns. Comparing states using a graph-theoretical approach, we confirmed that the structure of functional networks is preserved under our proposed anesthesia protocol but is lost using isoflurane alone at concentration levels greater than 1%. We believe that the widespread adoption of this protocol will be a step towards advancing translational neuroscience initiatives in non-human primate neuroimaging. To promote the collaborative use of neuroimaging resources, we openly share our datasets (https://zenodo.org/records/11118775).

Cannabis Use and Inhalational Anesthesia Administration in Older Adults: A Propensity-matched Retrospective Cohort Study.

Cannabis use is associated with higher intravenous anesthetic administration. Similar data regarding inhalational anesthetics are limited. With rising cannabis use prevalence, understanding any potential relationship with inhalational anesthetic dosing is crucial. Average intraoperative isoflurane or sevoflurane minimum alveolar concentration equivalents between older adults with and without cannabis use were compared. The electronic health records of 22,476 surgical patients 65 yr or older at the University of Florida Health System between 2018 and 2020 were reviewed. The primary exposure was cannabis use within 60 days of surgery, determined via (1) a previously published natural language processing algorithm applied to unstructured notes and (2) structured data, including International Classification of Diseases codes for cannabis use disorders and poisoning by cannabis, laboratory cannabinoids screening results, and RxNorm codes. The primary outcome was the intraoperative time-weighted average of isoflurane or sevoflurane minimum alveolar concentration equivalents at 1-min resolution. No a priori minimally clinically important difference was established. Patients demonstrating cannabis use were matched 4:1 to non-cannabis use controls using a propensity score. Among 5,118 meeting inclusion criteria, 1,340 patients (268 cannabis users and 1,072 nonusers) remained after propensity score matching. The median and interquartile range age was 69 (67 to 73) yr; 872 (65.0%) were male, and 1,143 (85.3%) were non-Hispanic White. The median (interquartile range) anesthesia duration was 175 (118 to 268) min. After matching, all baseline characteristics were well-balanced by exposure. Cannabis users had statistically significantly higher average minimum alveolar concentrations than nonusers (mean ± SD, 0.58 ± 0.23 vs. 0.54 ± 0.22, respectively; mean difference, 0.04; 95% confidence limits, 0.01 to 0.06; P = 0.020). Cannabis use was associated with administering statistically significantly higher inhalational anesthetic minimum alveolar concentration equivalents in older adults, but the clinical significance of this difference is unclear. These data do not support the hypothesis that cannabis users require clinically meaningfully higher inhalational anesthetics doses.

Effect of Atracurium and Rocuronium on the State and Response Entropy during Isoflurane Anesthesia: Randomized Prospective Study

Abstract Background Several researches have inspected the impact of inhalation anesthetics, intravenous anesthetics, and muscle relaxants on spectral entropy, but many didn’t evaluate the extent of neuromuscular block. Besides, they didn’t inspect the impact of distinct degrees of neuromuscular blockade on spectral entropy under dissimilar saturations of isoflurane inhalation. Hence, this study evaluated variant degrees of minimum alveolar concentration (MAC) to estimate the isoflurane concentration, along with various level of neuromuscular blockade. Aim of this study is to evaluate the effect of muscle relaxants (atracurium and rocuronium) on entropy readings (state, response entropy and response- state difference) during isoflurane anesthesia. This is a prospective randomized study where forty patients were included and divided into two study groups; patients in Group A received atracurium, while patients in Group R received rocuronium. State and response entropy were observed under MAC 0.8% and 1% under 50% and 100% neuromuscular blockage. Results There was a positive correlation between state (SE) and response entropy (RE) at baseline, different MAC, and different train of four (TOF) for both atracurium and rocuronium. State and response entropy decreased with increasing MAC of isoflurane (p &amp;lt; 0.001), while atracurium and rocuronium at TOF 50% and 100% showed no effect on SE or RE or RE-SE (P &amp;gt; 0.05). Conclusions State and response entropy can be used effectively to evaluate depth of anesthesia at different isoflurane MAC and atracurium or rocuronium doses. Registration number: ClinicalTrials.gov Identifier: NCT 05097508, Registered 5 October 2021 - prospectively registered, http://www.ClinicalTrial.gov

MiR-652-3p Suppressed the Protective Effects of Isoflurane Against Myocardial Injury in Hypoxia/Reoxygenation by Targeting ISL1.

This research is concentrated on investigating the role and mechanism of miR-652-3p in the protective effects of isoflurane (ISO) against myocardial ischemia-reperfusion (I/R) injury. H9c2 cells underwent pretreatment with varying concentrations of ISO, and subsequently, a hypoxia/reoxygenation (H/R) model was constructed. The levels of miR-652-3p, ISL LIM homeobox 1 (ISL1), and inflammatory cytokines interleukin (IL)-6 and tumor necrosis factor-alpha (TNF-α) were evaluated through reverse transcription polymerase chain reaction (RT-qPCR). Enzyme-linked immunosorbent assay was employed to investigate concentrations of myocardial injury markers, such as creatine kinase-MB (CK-MB) and cardiac troponin I (cTnI). Cell counting kit-8 was used to evaluate cell viability, while flow cytometry was utilized to measure apoptosis. Additionally, a dual luciferase reporter assay was conducted to validate the targeting relationship between ISL1 and miR-652-3p. Herein, we confirmed thatthe level of miR-652-3p wasgradually increased with prolonged hypoxia; nevertheless, this increase was suppressed by ISO pretreatment (P < 0.05). Additionally, ISO pretreatment prevented the decrease in cell viability, increase in apoptosis, and overproduction of IL-6, TNF-α, CK-MB, and cTnI induced by H/R (P < 0.05). However, the inhibitory effects of ISO were counteracted by the increased levels of miR-652-3p (P < 0.05). ISL1 is a potential target of miR-652-3p. H/R induction suppressed ISL1 levels compared to the control, but ISO treatment increased its expression (P < 0.05). Overexpression of ISL1 inhibited the elimination of the protective effect of ISO on myocardial damage induced by the elevation of miR-652-3p (P < 0.05). The findings of this research confirm that miR-652-3p attenuated the protective effect of ISO on cardiomyocytes in myocardial ischemia by targeting ISL1.

Effect of limb and cuff positioning on measurement of arterial blood pressure with an oscillometry device (PetMAP) in anaesthetized cats

Arterial blood pressure (ABP) is often measured with oscillometry during anaesthesia. Changing the height of the measuring cuff with respect to the level of the heart is known to affect oscillometry accuracy in some species; however, this effect has not been investigated in cats. The objective of this study was to determine the effects of raising and lowering the measuring cuff from standard position (level of the heart) on ABP, measured with PetMAP, in anaesthetised cats. ABP readings were obtained from 29 cats with the cuff at standard position (baseline), and 5 cm above and below the heart. The end-tidal isoflurane concentrations were maintained constant during data acquisition. There were no differences between baseline values and those measured below the heart, while ABP measured above the heart was consistently lower than baseline for both the thoracic and pelvic limbs (P < 0.001), with absolute differences of 8.2 (2.5 – 14) mmHg and 6.5 (3.0 – 15.0) mmHg, respectively. Systolic ABP readings at the pelvic limb were consistently higher than those at the thoracic limb at standard position (112 ± 26 versus 103 ± 21 mmHg, p = 0.010), above (106 ± 22 versus 95 ± 20 mmHg, p = 0.003), and below the heart (116 ± 26 versus 107 ± 22 mmHg, p = 0.011). This study shows that raising the cuff by 5 cm above the heart, which may become necessary during procedural positioning, results in clinically significant underestimation of ABP measured with PetMAP.

Isoflurane Preconditioning Alleviates Hypoxia/Reoxygenation-Induced Cardiomyocyte Injury by Inhibiting miR-195-3p Expression.

To investigate the role of microRNA-195-3p (miR-195-3p) in hypoxia/reoxygenation (H/R)-induced cardiomyocyte injury. AC16 human cardiomyocyte cells were cultured and pretreated with different concentrations of isoflurane (ISO) (1%, 2%, and 3%), followed by 6h each of hypoxia and reoxygenation to construct H/R cell models. The optimum ISO concentration was assessed based on the cell viability. miR-195-3p expression was regulated by in vitro celltransfection. Cell viability was determined by MTT assay, and apoptosis was evaluated by flow cytometry. The levels of myocardial injury and inflammation were determined by enzyme-linked immunosorbent assay. Compared with the control group, the cell viability of the H/R group had significantly decreased and that of ISO pretreatment had increased in a dose-dependent manner. Therefore, we selected a 2% ISO concentration for pretreatment. MiR-195-3p expression had significantly increased in the H/R group and decreased after 2% ISO pretreatment. Additionally, the number of apoptotic cells and the levels of lactate dehydrogenase, creatine kinase-myoglobin binding, cardiactroponin I, interleukin (IL)-1β, IL-6, and tumor necrosis factor-α had increased significantly. ISO preconditioning inhibited H/R-induced AC16 cell damage, whereas miR-195-3p overexpression reversed the protective effects of ISO on cardiomyocytes. The expression of phosphatase and tensin homolog deleted on chromosome 10 (PTEN) was reduced in the H/R-induced AC16 cells, and PTEN is a downstream target gene of miR-195-3p. Preconditioning with 2% ISO plays a protective role in H/R-induced AC16 cell damage by inhibiting miR-195-3p expression.

The effect of oral pregabalin on the minimum alveolar concentration of isoflurane in cats

ObjectiveTo investigate the effect of three different doses of oral pregabalin on minimum alveolar concentration of isoflurane (MACISO) in cats. Study designProspective, randomized, placebo-controlled, blinded, crossover trial. AnimalsA group of eight healthy adult cats aged 24–48 months. MethodsCats were randomly assigned to three oral doses of pregabalin (low dose: 2.5 mg kg–1, medium dose: 5 mg kg–1, high dose: 10 mg kg–1) or placebo 2 hours before MACISO determination, with the multiple treatments administered with a minimum 7 day washout period. Anesthesia was induced and maintained with isoflurane in oxygen until endotracheal intubation was achieved, and maintained with isoflurane with volume-controlled ventilation. MACISO was determined in triplicate using the bracketing technique and tail clamp method 120 minutes after pregabalin or placebo administration. Physiologic variables (including heart rate and blood pressure) recorded during MACISO determination were averaged and compared between the pregabalin and placebo treatments. One-way analysis of variance and the Friedman test were used to assess the difference for normally and non-normally distributed data, respectively. The Tukey test was used as a post hoc analysis. Values of p < 0.05 were considered significant. ResultsThe MACISO with the medium- and high-dose pregabalin treatments were 1.33 ± 0.21% and 1.23 ± 0.17%, respectively. These were significantly lower than MACISO after placebo treatment (1.62 ± 0.13%; p = 0.014, p < 0.001, respectively), representing a decrease of 18 ± 9% and 24 ± 6%. The mean plasma pregabalin concentration was negatively correlated with MACISO values. Physiologic variables did not differ significantly between treatments. Conclusions and clinical relevanceDoses of 5 or 10 mg kg–1 pregabalin, administered orally 2 hours before determining MACISO, had a significant isoflurane-sparing effect in cats.

Genotype- and sex-specific changes in vital parameters during isoflurane anesthesia in a mouse model of Alzheimer's disease.

The prevalence of neurodegenerative diseases is increasing as is life expectancy with Alzheimer's disease accounting for two-thirds of dementia cases globally. Whether general anesthesia and surgery worsen cognitive decline is still a matter of debate and most likely depending on the interplay of various influencing factors. In order to account for this complexity, Alzheimer's disease animal models have been developed. The Tg2576 model of Alzheimer's disease is a well-established mouse model exhibiting amyloidopathy and age-dependent sex-specific differences in Alzheimer's disease symptomology. Yet, data on anesthesia in this mouse model is scarce and a systematic comparison of vital parameters during anesthesia with wild-type animals is missing. In order to investigate the safety of general anesthesia and changes in vital parameters during general anesthesia in Tg2576 mice, we did a secondary analysis of vital parameters collected during general anesthesia in aged Tg2576 mice. After governmental approval (General Administration of the Free State of Bavaria, file number: 55.2-1-54-2532-149-11) 60 mice at 10-12 months of age were exposed to isoflurane (1.6 Vol%) for 120 min, data of 58 mice was analyzed. During general anesthesia, heart rate, respiratory rate, temperature, isoflurane concentration and fraction of inspired oxygen were monitored and collected. Data were analyzed using univariate and multivariate linear mixed regression models. During general anesthesia, heart rate decreased in a sex-specific manner. Respiratory rate decreased and body temperature increased dependent on genotype. However, the changes were limited and all vital parameters stayed within physiological limits. Isoflurane anesthesia in the Tg2576 mouse model is safe and does not seem to influence experimental results by interacting with vital parameters. The present study provides information on appropriate anesthesia in order to advance research on anesthesia and AD and could contribute to improving laboratory animal welfare.

Intraoperative Isoflurane End-Tidal Concentration during Infusion of Fentanyl, Tramadol, or Fentanyl-Tramadol Combination in Cats.

The aim of this study was to evaluate the end-tidal concentration of isoflurane required, clinical parameters, intraoperative antinociceptive effect, and postoperative analgesia in cats undergoing ovariohysterectomy, receiving fentanyl, tramadol, or fentanyl/tramadol. Sixty-six cats in three groups, were premedicated with dexmedetomidine and infused with one of the following treatments: fentanyl, tramadol, or fentanyl/tramadol combination. Anesthesia was induced with alfaxolone and maintained with isoflurane, titrated to keep heart rate, respiratory rate and systolic arterial pressure within target values recorded at endotracheal intubation. An intraoperative cumulative scale was performed. Postoperatively, a short form of the Glasgow Composite Measure Pain Scale Feline was used at 2, 12, and 24 h. The groups were similar for age, weight, dose of dexmedetomidine, and alfaxalone administered. A greater reduction in the end-tidal isoflurane fraction was observed with the combined fentanyl/tramadol infusion than with either fentanyl or tramadol alone. No differences in the end-tidal isoflurane fraction were found between fentanyl or tramadol alone. Hemodynamic stability associated with minimal cardiopulmonary changes, low response to noxious intraoperative stimulation, and low postoperative pain scores were also observed with the fentanyl/tramadol combination. The fentanyl/tramadol combination provided a reduction in the end-tidal isoflurane fraction compared with fentanyl or tramadol alone.

Minimum anesthetic concentration of isoflurane and sevoflurane and cardiorespiratory effects of varying inspired oxygen fractions in Magellanic penguins (Spheniscus magellanicus).

The aim of this study was to determine the minimum anesthetic concentration of isoflurane (MACISO) and sevoflurane (MACSEVO) and evaluate the cardiorespiratory changes induced by varying fractions of inspired oxygen (FiO2) in Magellanic penguins (Spheniscus magellanicus). Twenty adult penguins (3.53 ± 0.44kg) of undetermined sex were used. Both MACISO (n = 9) and MACSEVO (n = 13) were established using an up-and-down design. Next, twelve mechanically ventilated penguins were maintained at 1 MACISO or 1 MACSEVO (n = 6 per group) with the FiO2 initially set at 1.0. Three FiO2 values (0.6, 0.4 and 0.2) were then held constant during anesthesia for 20minutes each. Arterial blood samples were collected for gas analysis after the 20-minute period for each FiO2. Mean± SD MACISO was 1.93 ± 0.10% and MACSEVO was 3.53 ± 0.13%. Other than heart rate at 0.6 FiO2 (86 ± 11 beats/minute in MACISO and 132 ± 37 beats/minute in MACSEVO; p = 0.041), no significant cardiorespiratory differences were detected between groups. In both groups, decreasing the FiO2 produced increased pH values and reduced partial pressures of carbon dioxide and bicarbonate. Partial pressures of oxygen (PaO2) gradually lowered from 1.0 FiO2 through 0.2 FiO2, though hypoxemia (PaO2 < 80mmHg) occurred only with the latter FiO2. The MACISO and the MACSEVO for the Magellanic penguin fell within the upper range of reported avian MAC estimates. To prevent hypoxemia in healthy, mechanically ventilated, either isoflurane- or sevoflurane-anesthetized Magellanic penguins, a minimum FiO2 of 0.4 should be used.

Comparison of analgesic efficacy of tramadol, morphine and methadone in cats undergoing ovariohysterectomy.

The aim of this study was to compare the analgesic efficacy and the effect on physiological variables and behavior of the use of tramadol, methadone and morphine as preoperative analgesia in healthy cats undergoing elective ovariohysterectomy. Cats undergoing ovariohysterectomy were randomly assigned to receive one of the following premedication treatments intramuscularly: methadone (0.2 mg/kg; n = 10); morphine (0.2 mg/kg; n = 10); or tramadol (3 mg/kg; n = 10). Induction of anesthesia was done with propofol, and maintenance of anesthesia was done with isoflurane. Intraoperative heart rate, arterial blood pressure, respiratory rate, end-tidal isoflurane concentration and frequency of rescue analgesia (fentanyl 2.5 µg/kg) were compared between groups. Postoperative analgesia was assessed using the UNESP-Botucatu Multidimensional Composite Pain Scale, and perioperative serum glucose, cortisol concentrations and postoperative rescue analgesia were evaluated. Intraoperative rescue analgesia was required in 76.5% of cats at some time during surgery, and 27% of cats required postoperative rescue analgesia up to 6 h after extubation. There were no significant differences between groups with respect to intraoperative and postoperative rescue analgesia, pain scale scores and end-tidal isoflurane concentrations. In the immediate postoperative period, after extubation, most of the patients presented with hypothermia; however, 1-6 h postoperatively, hyperthermia was observed in most of the patients, and was most common in the tramadol group. Under the conditions of this study, methadone, morphine and tramadol produced satisfactory postoperative analgesia in most of the cats undergoing ovariohysterectomy, and the effects lasted up to 6 h postoperatively. Intraoperative analgesia was not sufficient in most cases. Significant cardiovascular or respiratory effects contraindicating the use of these drugs were not found. Postanesthetic hyperthermia occurred with all opioids studied and was more frequent in the tramadol group.