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Objective To determine the effect of fentanyl on the minimum alveolar concentration of isoflurane (MACISO) and cardiovascular variables in dogs, and how the treatment of bradycardia affects them. Study design Prospective, randomized crossover-controlled trial. Animals A total of six male Beagle dogs weighing 9.9 ± 0.7 kg (mean ± standard deviation) and aged 13 months. Methods To each dog, two treatments were assigned on different days: fentanyl (FENTA) or fentanyl plus glycopyrrolate (FENTAglyco) to maintain heart rate (HR) between 100 and 132 beats minute−1. Determinations of MACISO were performed with 10 plasma fentanyl target concentrations ([Fenta]Target (0, 0.16, 0.32, 0.64, 1.25, 2.5, 5.0, 10.0, 20.0 and 40.0 ng mL−1) for FENTA and 5 [Fenta]Target (0, 1.25, 2.5, 5.0, 10.0 ng mL−1)) for FENTAglyco. During each MACISO determination, cardiovascular variables [mean arterial pressure (MAP), HR and cardiac index (CI)] were measured, and systemic vascular resistance index (SVRI) calculated. Pharmacodynamic models were used to describe the plasma fentanyl concentration [Fenta]–response relationship for the effect on MACISO and cardiovascular variables. A mixed-model analysis of variance followed by Dunnett’s or Tukey’s test, and the Bonferroni adjustment were used for comparisons within and between each treatment, respectively. Significance was set as p Results Fentanyl decreased MACISO by a maximum of 84%. The [Fenta] producing 50% decrease in MAC, HR and CI were 2.64, 3.65 and 4.30 ng mL−1 (typical values of population model), respectively. The prevention of fentanyl-mediated bradycardia caused no significant effect on MACISO, but increased HR, MAP and CI, and decreased SVRI when compared with isoflurane alone. Conclusions and clinical relevance Fentanyl caused a plasma concentration-dependent decrease in MACISO, HR and CI and an increase in SVRI. Cardiovascular improvements associated with fentanyl in isoflurane-anesthetized dogs only occurred when the fentanyl-mediated bradycardia was prevented.

Objective To compare the effects of sevoflurane, propofol and alfaxalone on the neuromuscular blockade induced by a single intravenous bolus of rocuronium in dogs. Study design A randomized, prospective, crossover experimental study. Animals A total of eight adult Beagle dogs (four female, four male), weighing 8.9–15.3 kg and aged 5–7 years. Methods The dogs were anesthetized three times with 1.25× minimum alveolar concentration of sevoflurane (SEVO treatment) and 1.25× minimum infusion rate of propofol (PROP treatment) or alfaxalone (ALFX treatment) at intervals of ≥14 days. Neuromuscular function was monitored with train-of-four (TOF) stimulation of the peroneal nerve by acceleromyography. After recording the control TOF ratio (TOFRC), a single bolus dose of rocuronium (1 mg kg–1) was administered intravenously. The times from rocuronium administration to achieving TOF count 0 (onset time), from achieving TOF count 0 to the reappearance of TOF count 4 (clinical blockade period), from 25% to 75% of TOFRC (recovery index) and from achieving TOF count 0 to TOF ratio/TOFRC >0.9 (total neuromuscular blockade duration) were recorded. Results The onset time and recovery index did not differ among the treatments. The median clinical blockade period was longer in the SEVO treatment [27.3 (26.0–30.3) minutes] than in PROP [16.6 (15.4–18.0) minutes; p = 0.002] and ALFX [22.4 (18.6–23.1) minutes; p = 0.017] treatments; and longer in the ALFX treatment than in the PROP treatment (p = 0.020). The mean total neuromuscular blockade duration was longer in the SEVO treatment (43.7 ± 9.9 minutes) than in PROP (25.1 ± 2.7 minutes; p Conclusions and clinical relevance Compared with alfaxalone and propofol, sevoflurane prolonged rocuronium-induced neuromuscular blockade by a significantly greater extent in dogs.

Here is presented, in chronological order, the studies that established the standards and determined the parameters currently considered for the safe use of anesthetic agents administered by intravenous or inhalation routes. The methods used in the experimental settings, as well as the modifications in the protocols to adapt to different clinical conditions, are described and discussed; The pharmacological criteria and the impact of these anesthetics on the cardiovascular and pulmonary systems are highlighted. However, additional information regarding the mechanisms of action of such agents is still needed, which would improve their use in terms of safety and efficacy.

BACKGROUND: Endoscopic rhinosinus surgery in children is associated with a high anesthetic risk because of intraoperative stress. This study aimed to, considering the dynamic picture of the biochemical markers of surgical stress, to assess the effectiveness of regional methods of combined anesthesia in rhinosinus surgery in children. MATERIALS AND METHODS: A comparative study was conducted in parallel groups composed of 100 patients aged 617 years who had undergone an assessment of their physical condition using the ASA I-II scales and planned endoscopic endonasal surgery lasting up to 2 h under combined anesthesia. In all groups, the introductory anesthesia was combined, i.e., inhalation of sevoflurane in an oxygenair mixture in combination with intravenous administration of propofol. To ensure the patency of the respiratory tract, endotracheal anesthesia was administered. Patients were divided into two groups of 50 people each, depending on the method of maintaining anesthesia. Group 1 received inhalation of sevoflurane in an airoxygen mixture with a target value of the minimum alveolar concentration of (MAC) 0.70.9, and regional blockage was performed bilaterally, i.e., pterygopalatine anesthesia with palatine access (palatinal) and infra-orbital intraoral access with ropivacaine solution. Group 2 received inhalation of sevoflurane in an airoxygen mixture with a target value of 1.5 МАС, and 5% tramadol solution was used intravenously for analgesia. RESULTS: Data on the dynamics of glucose, lactate, and cortisol levels in both groups proved the effectiveness and stability of the anesthesia methods used. However, the concentration of the inhaled anesthetic agent in the tramadol group was used was twice as high as the concentration in the regional anesthetic group. DISCUSSION: The dynamics and deviations of biochemical markers of surgical stress were not significantly different in the intergroup and intragroup interstage parameters beyond the reference values. CONCLUSIONS: The proposed anesthesia methods did not induce stress reactions to surgical intervention, and the anesthesia methods in both groups were adequate and effective.

What is known and objective Remifentanil can effectively decrease the sevoflurane concentration to block sympathetic adrenergic response to CO2 pneumoperitoneum stimulus,and liver dysfunction will significantly reduce the MACBAR (minimum alveolar concentration for blocking adrenergic response) of sevoflurane. However, the effects of different remifentanil concentrations on the MACBAR of sevoflurane in patients with liver dysfunction are unclear. The aim of this study was to observe the effects of different remifentanil concentrations by intravenous target-controlled infusion on the MACBAR of sevoflurane in patients with grade B liver dysfunction under carbon dioxide pneumoperitoneum stimulus. Methods Seventy-five patients with grade B liver dysfunction undergoing elective laparoscopic surgery were selected, and randomly divided into three groups with remifentanil plasma target concentrations of 0 (group R0 ), 1 (group R1 ) and 2 (group R2 ) ng/ml. Anaesthesia was induced by intravenous injection of propofol 2-3 mg/kg, remifentanil 2 μg/kg and cisatracurium 0.15 mg/kg. All groups were inhaled different concentrations of sevoflurane. The determination of sevoflurane MACBAR in each group was used a method of sequential-allocation technique, and venous blood samples were taken before and after the creation of carbon dioxide pneumoperitoneum to determine plasma adrenaline and noradrenaline concentrations. Results and discussions The MACBAR of sevoflurane in groups R0 , R1 and R2 was 4.83%, 3.00% and 2.10%, respectively. The MACBAR of sevoflurane was significantly difference among the three groups. When a similar effect of MACBAR had achieved in each group, no significant differences were found in the changes of plasma adrenaline and noradrenaline concentrations before and after the creation of pneumoperitoneum. What is new and conclusion Target-controlled infusion of different concentrations of remifentanil can reduce sevoflurane MACBAR during pneumoperitoneum stimulation in patients with liver dysfunction in some degree. However, the changes of plasma adrenaline and noradrenaline concentrations are consistent in the three groups when patient's stress response was inhibited at the same degree.

Background To investigate the effects of different plasma target concentrations of remifentanil on the minimum alveolar concentration (MAC) for blocking adrenergic response (BAR) of sevoflurane in children with laparoscopic herniorrhaphy. Methods Seventy-five children with 3-7 years old scheduled for laparoscopic herniorrhaphy were randomly divided into group R0, group R1, and group R2 according to different remifentanil plasma target concentration (0, 1, and 2 ngml-1), respectively. The MACBAR of sevoflurane was determined by the up-and-down and sequential method in each group. The concentrations of epinephrine and noradrenaline were also determined at corresponding time points. Results A total of 52 child patients were used among the anticipated 75 patients. In groups R0, R1, and R2, the MACBAR of sevoflurane was (3.29 ± 0.17) %, (2.12 ± 0.10) % and (1.29 ± 0.11) %, respectively, and a significant difference was found among the three groups (P Conclusion Remifentanil by target-controlled infusion can effectively reduce the MACBAR of sevoflurane during laparoscopic surgery in children. At a similar effect of MACBAR, both the changes of epinephrine and noradrenaline concentrations are not affected by the infusion of different remifentanil target concentrations. Trial registration The trial was registered at http://www.chictr.org.cn(ChiCTR1800019393, 8, Nov, 2018).

BackgroundIn the era of enhanced recovery after surgery, there is significant discussion regarding the impact of intraoperative anesthetic management on short-term outcomes following liver transplantation (LT), with no clear consensus in the literature.ObjectivesTo identify whether or not intraoperative anesthetic management affects short-term outcomes after liver transplantation.Data sourcesOvid MEDLINE, Embase, Scopus, Google Scholar, and Cochrane Central.MethodsA systematic review following PRISMA guidelines was undertaken. The systematic review was registered on PROSPERO (CRD42021239758). An international expert panel made recommendations for clinical practice using the GRADE approach.ResultsAfter screening, 14 studies were eligible for inclusion in this systematic review. Six were prospective randomized clinical trials, three were prospective nonrandomized clinical trials, and five were retrospective studies. These manuscripts were reviewed to look at five questions regarding anesthetic care and its impact on short term outcomes following liver transplant. After review of the literature, the quality of evidence according to the following outcomes was as follows: intraoperative and postoperative morbidity and mortality (low), early allograft dysfunction (low), and hospital and ICU length of stay (moderate).ConclusionsFor optimal short term outcomes after liver transplantation, the panel recommends the use of volatile anesthetics in preference to total intravenous anesthesia (TIVA) (Level of Evidence: Very low; Strength of Recommendation: Weak) and minimum alveolar concentration (MAC) versus bispectral index (BIS) for depth of anesthesia monitoring (Level of Evidence: Very low; Strength of Recommendation: Weak). Regarding ventilation and oxygenation, the panel recommends a restrictive oxygenation strategy targeting a PaO2 of 70-120mmHg (10-14kPa), a tidal volume of 6-8ml/kg ideal body weight (IBW), administration of positive end expiratory pressure (PEEP) tailored to patient intraoperative physiology, and recruitment maneuvers. (Level of evidence: Very low; Strength of Recommendation: Strong). Finally, the panel recommends the routine use of antiemetic prophylaxis. (Level of evidence: low; Strength of Recommendation: Strong).

The aim of the stady wos to investigate the mechanisms of suppression of cerebral bioelectrical activity under adverse effects caused by neurotoxicants using inhalation anesthesia with sevoflurane. The research included 19 cases (male/female 12/7, aged 19—55, BMIs under 35) with intracerebral tumors. Patients were under medical observation and neurosurgical treatment. Invasive procedures were carried out under sevoflurane-based general anesthesia with a dose of anesthetic varying from 0,8 to 1,3 MAC (minimum alveolar concentration). Technologically advanced neurosurgical procedures involved neurophysiological polymodal monitoring, which included EEG and ECoG testing. Probit analysis results showed that, with cerebral cortex bioelectrical activity suppression index equal to 32±8%, nearly half the cases displayed a formation of an «outburst-suppression» type of pattern on the scalp EEG. The condition for half the cases displaying a formation of this type of periodic pattern is the suppression index equaling 58±7% on ECoG. Space-and-time evolution of suppression patterns, formed on the cerebral cortex, is the main reason for persistence of uninterrupted activity on EEG. The obtained results allow to further define principles of neurodynamics, which apply to acute intoxication with neurotoxicants. With regard to relative similarity of intoxication-induced coma cases, registration of periodic EEG patterns even with a low suppression index indicates a more severe form of cerebral insufficiency.

Objective To evaluate the effects of combined infusions of vatinoxan and dexmedetomidine on inhalant anesthetic requirement and cardiopulmonary function in dogs. Study design Prospective experimental study. Methods A total of six Beagle dogs were anesthetized to determine sevoflurane minimum alveolar concentration (MAC) prior to and after an intravenous (IV) dose (loading, then continuous infusion) of dexmedetomidine (4.5 mu g kg(-1) hour(-1)) and after two IV doses of vatinoxan in sequence (90 and 180 mu g kg(-1) hour(-1)). Blood was collected for plasma dexmedetomidine and vatinoxan concentrations. During a separate anesthesia, cardiac output (CO) was measured under equivalent MAC conditions of sevoflurane and dexmedetomidine, and then with each added dose of vatinoxan. For each treatment, cardiovascular variables were measured with spontaneous and controlled ventilation. Repeated measures analyses were performed for each response variable; for all analyses, p 180 mu g kg(-1) hour(-1) might improve cardiovascular function further in combination with this dose of dexmedetomidine, but beneficial effects on anesthesia plane and recovery quality may be lost.

Oxygen supplementation is rarely considered when anesthetizing laboratory mice, despite reports that mice become profoundly hypoxic under anesthesia. Little is known about the effects of hypoxia on anesthetic performance. This article focuses on the effects of oxygen supplementation on physiologic parameters and depth of anesthesia in male and female C57BL/6 mice. Anesthesia was performed via common injectable anesthetic protocols and with isoflurane. Mice anesthetized with injectable anesthesia received one of 3 drug protocols. Low-dose ketamine/xylazine (100/8 mg/kg) was chosen to provide immobilization of mice, suitable for imaging procedures. Medium-dose ketamine/xylazine/acepromazine (100/10/1 mg/kg) was chosen as a dose that has been recommended for surgical procedures. High-dose ketamine/xylazine/acepromazine (150/12/3 mg/kg) was chosen after pilot studies to provide a long duration of a deep plane of anesthesia. We also tested the effects of oxygen supplementation on the minimum alveolar concentration (MAC) of isoflurane in mice. Mice breathed supplemental 100% oxygen, room air, or medical air with 21% oxygen. Anesthetized mice that did not receive supplemental oxygen all became hypoxic, while hypoxia was prevented in mice that received oxygen. Oxygen supplementation did not affect the MAC of isoflurane. At the high injectable dose, all mice not receiving oxygen supplementation died while all mice receiving oxygen supplementation survived. At low and medium doses, supplemental oxygen reduced the duration of the surgical plane of anesthesia (low dose with oxygen: 22 ± 14 min; low dose without supplementation: 29 ± 18 min; medium dose with oxygen: 43 ± 18 min; medium dose without supplementation: 61 ± 27 min). These results suggest that mice anesthetized with injectable and inhalant anesthesia without supplemental oxygen are routinely hypoxic. This hypoxia prolongs the duration of anesthesia with injectable drug protocols and affects survival at high doses of injectable anesthetics. Because of variable responses to injectable anesthetics in mice, oxygen supplementation is recommended for all anesthetized mice.

Background and Aims: We hypothesized that maintaining a patient on moderate–high doses of potent inhalational agent for greater than 30 min during the post-bypass period would be an independent predictor of initiation and usage of either inotropic and/or vasopressor infusions. Setting and Design: This study is a retrospective design and approved by the institutional review board. The setting was a single-center, academic tertiary care hospital in Detroit, Michigan. Materials and Methods: Three-hundred, ninety-seven elective cardiac surgery patients were identified for chart review. Electronic medical records were reviewed to collect demographics and perioperative data. Statistics used include a propensity score regression adjusted analysis utilizing logistic regression models and a multivariable model. Results: A propensity score regression adjusted analysis was performed and then applied in both univariate and multivariate logistic regression models with a p value of &lt, 0.05 reaching statistical significance. Fifty-six percent of the participants had an exposure of greater than 30 min of a minimum alveolar concentration of isoflurane greater than 0.5 (ETISO ≥ 0.5MAC, 30 min) in the post-bypass period. After adjusting for propensity score, this was found to be a significant predictor of inotrope and/or vasoconstrictor use post-bypass (OR 2.49, 95% CI 1.15–5.38, p = 0.021). In the multivariate model, pulmonary hypertension (OR 5.9, 95% CI 1.33–26.28, p = 0.02), Euroscore II (2.73, 95% CI 1.35–5.5, p = 0.005), and cardiopulmonary bypass hours (OR 1.86, 95% CI 1.02–3.4, p = 0.042) emerged as significant. Conclusions: This study showed that an ETISO ≥ 0.5MAC, 30 min exposure during the immediate post-bypass period during elective cardiac surgery was an independent predictor of a patient being started on inotrope or vasoconstrictor infusions. Further research should consider a prospective design and examine depth of anesthesia during the post-bypass period.

Background The bispectoral index (BIS), a parameter derived from electroencephalogram, has been used to assess the depth of anesthesia. The objectives of this study were to evaluate the effect of BIS monitoring on sevoflurane consumption and recovery profile at the end of anesthesia. After obtaining Institutional Review Board approval and written informed consent, 25 American Society of Anesthesiologists (ASA) physical status classification 1 and 2 patients undergoing breast cancer surgeries who had BIS monitoring in addition to standard ASA monitoring (BIS GROUP) were compared against 25 controls (control group). In the control group, adequate depth of anesthesia was maintained using routine clinical parameters like heart rate (HR), mean arterial pressure (MAP), and minimum alveolar concentration (MAC) of sevoflurane, while in the BIS group, it was maintained by keeping the BIS score between 40 and 60 (mean 50). Data including demographics, sevoflurane consumption, hemodynamic variables, and recovery profile at the end of anesthesia was assessed in terms of time for eye opening (TEO), time for motor response (TMR), time for extubation (TE), and modified Aldrete scoring (MAS). Results The mean sevoflurane consumption was lower (P = 0.019) in the BIS group. TEO (P = 0.001), TMR (P = 0.0001), and TE (0.003) were shorter in the BIS group. Difference in MAS between the 2 groups was not statistically significant (P = 0.085). Conclusions BIS monitoring during anesthesia resulted in significant reduction in the sevoflurane consumption. Patients who had BIS monitoring awoke earlier and had better recovery profile at the end of anesthesia.

Analysis of peripheral venous pressure (PVP) waveforms is a novel method of monitoring intravascular volume. Two pediatric cohorts were studied to test the effect of anesthetic agents on the PVP waveform and cross-talk between peripheral veins and arteries: (1) dehydration setting in a pyloromyotomy using the infused anesthetic propofol and (2) hemorrhage setting during elective surgery for craniosynostosis with the inhaled anesthetic isoflurane. PVP waveforms were collected from 39 patients that received propofol and 9 that received isoflurane. A multiple analysis of variance test determined if anesthetics influence the PVP waveform. A prediction system was built using k-nearest neighbor (k-NN) to distinguish between: (1) PVP waveforms with and without propofol and (2) different minimum alveolar concentration (MAC) groups of isoflurane. 52 porcine, 5 propofol, and 7 isoflurane subjects were used to determine the cross-talk between veins and arteries at the heart and respiratory rate frequency during: (a) during and after bleeding with constant anesthesia, (b) before and after propofol, and (c) at each MAC value. PVP waveforms are influenced by anesthetics, determined by MANOVA: p value η2 = 0.478 for hypovolemic, and η2 = 0.388 for euvolemic conditions. The k-NN prediction models had 82% and 77% accuracy for detecting propofol and MAC, respectively. The cross-talk relationship at each stage was: (a) ρ = 0.95, (b) ρ = 0.96, and (c) could not be evaluated using this cohort. Future research should consider anesthetic agents when analyzing PVP waveforms developing future clinical monitoring technology that uses PVP.

The aim of this study was to compare changes in tissue blood flow and tissue oxygen tension in the masseter muscle and mandibular bone marrow induced by remifentanil under desflurane or sevoflurane anesthesia. Eleven male tracheotomized Japan White rabbits were anesthetized with desflurane or sevoflurane under mechanical ventilation. The order of the inhalation of desflurane or sevoflurane was randomized. Desflurane or sevoflurane was administered at 1.0 minimum alveolar concentration and remifentanil was infused at 0.4 µg/kg/min. Observed variables included heart rate (HR), blood pressure (BP), common carotid artery blood flow (CCBF), mandibular bone marrow tissue blood flow (BBF), masseter muscle tissue blood flow (MBF), mandibular bone marrow tissue oxygen tension (PbO2), and masseter muscle tissue oxygen tension (PmO2). Two way repeated measures ANOVA showed no interaction between volatile anesthetics and remifentanil infusion except for MBF. There were significant differences in HR, SBP, DBP, MAP and CCBF between desflurane and sevoflurane groups. There were also significant differences in HR, SBP, DBP, MAP, CCBF, BBF and PbO2 before, during and after remifentanil infusion. Desflurane reduced tissue blood flow in the masseter muscle and mandibular bone marrow while better maintained HR and BP than sevoflurane. Under remifentanil infusion, although both anesthetics reduced tissue blood flow, tissue oxygen tension was maintained in masseter muscle and mandibular bone marrow.

We evaluated changes in cardiovascular and renal functions as well as arginine vasopressin (AVP) secretion, with remifentanil and dexmedetomidine administration alone or in combination in sevoflurane-anesthetized dogs. Six healthy adult Beagle dogs received one of the following four treatments in a randomized crossover study: saline (C), remifentanil alone at successively increasing doses (R; 0.15, 0.60, and 2.40 µg/kg/min), dexmedetomidine alone (D; 0.5 µg/kg intravenously for initial 10 min followed by a constant rate infusion at 0.5 µg/kg/hr), and a combination of remifentanil and dexmedetomidine at the above-mentioned doses (RD). Sevoflurane doses were adjusted to 1.5 times of minimum alveolar concentration (MAC) equivalent according to MAC-sparing effects with remifentanil and dexmedetomidine as previously reported. Cardiovascular measurements, renal function data, and plasma AVP concentrations were determined before and every 60 min until 180 min after drug administration as per each treatment. In the R, D and RD, heart rate significantly decreased and mean arterial pressure significantly increased from baseline or with C. Cardiac index significantly decreased and systemic vascular resistance index increased with D and RD. Oxygen extraction ratio, renal blood flow, and glomerular filtration rate were not affected. The plasma AVP concentrations significantly decreased in D and RD, but increased in R. Only in D, the natriuresis was elicited. The combination of remifentanil and dexmedetomidine in sevoflurane-anesthetized dogs was acceptable in terms of the hemodynamics, oxygenation, and renal function. Remifentanil may interfere with dexmedetomidine-induced diuresis and inhibition of AVP secretion.

Relevance. The increase in the number of severe brain injuries due to stroke and traumatic brain injury determines the need to study and develop effective strategies for neuroprotection. The article highlights new mechanisms of the neuroprotective action of the inhalation anesthetic xenon based on the data of our own experimental studies.Aim of study. To assess the effect of anesthesia with xenon at a concentration of 0.5 MAC (minimum alveolar concentration) on the phosphorylation of glycogen synthase kinase 3β (GSK-3β) and the content of antioxidant defense enzymes in the rat brain.Material and methods. The effect of inhalation anesthesia with xenon on the phosphorylation of the GSK-3β enzyme in comparison with lithium chloride, as well as on the content of heme oxygenase, catalase, and Mn-superoxide dismutase in rat brain homogenates was studied by immunoblotting.Results. The use of xenon at a concentration of 0.5 MAA causes an almost twofold increase in the content of the phosphorylated form of the GSK-3β enzyme in comparison with the control (pConclusion. The conducted experimental study revealed new molecular mechanisms of action of the inhalation anesthetic xenon. The effect of xenon on the pool of enzymes involved in the protection of the brain from oxidative distress was found. The data obtained indicate the prospects for using xenon and require further research in this direction. The use of xenon at a concentration of 50 vol.% (0.5 MAA) for 30 minutes does not affect the content of the glycogen synthase-3β enzyme, at the same time causing an almost twofold increase in its phosphorylated form, the glycogen synthase-3β enzyme, and is accompanied by a significant increase the content of heme oxygenase, Mn-superoxide dismutase and a slight increase in the content of catalase in rat brain homogenates. Thus, the results of the study suggest that one of the possible mechanisms of the neuroprotective effect of xenon is the phosphorylation of glycogen synthase-3β, which prevents the opening of the mitochondrial pore, inhibiting the death of mitochondria-mediated apoptosis of neurons and increasing the level of antioxidant protection in them.

To identify the better volatile anaesthetic delivery system in an intensive care setting, we compared the circle breathing system and two models of reflection systems (AnaConDa™ with a dead space of 100 ml (ACD-100) or 50 ml (ACD-50)). These systems were analysed for the parameters like wash-in, consumption, and wash-out of isoflurane and sevoflurane utilising a test lung model. The test lung was connected to a respirator (circle breathing system: Aisys CS™; ACD-100/50: Puriton Bennett 840). Set parameters were volume-controlled mode, tidal volume-500 ml, respiratory rate-10/min, inspiration time-2 sec, PEEP-5 mbar, and oxygen-21%. Wash-in, consumption, and wash-out were investigated at fresh gas flows of 0.5, 1.0, 2.5, and 5.0 l/min. Anaesthetic target concentrations were 0.5, 1.0, 1.5, 2.0, and 2.5%. Wash-in was slower in ACD-100/-50 compared to the circle breathing system, except for fresh gas flows of 0.5 and 1.0 l/min. The consumption of isoflurane and sevoflurane in ACD-100 and ACD-50 corresponded to the fresh gas flow of 0.5-1.0 l/min in the circle breathing system. Consumption with ACD-50 was higher in comparison to ACD-100, especially at gas concentrations > 1.5%. Wash-out was quicker in ACD-100/-50 than in the circle breathing system at a fresh gas flow of 0.5 l/min, however, it was longer at all the other flow rates. Wash-out was comparable in ACD-100 and ACD-50. Wash-in and wash-out were generally quicker with the circle breathing system than in ACD-100/-50. However, consumption at 0.5 minimum alveolar concentration was comparable at flows of 0.5 and 1.0 l/min.

Isoflurane is an inhaled anesthetic, though its actions at the cellular level remain controversial. By using acute spinal cord slices from adult rats and the whole-cell recording technique, we found that aqueous isoflurane at the minimum alveolar concentration decreased postsynaptic neural excitability and enhanced membrane conductance, while suppressing glutamate release from presynaptic afferent onto substantia gelatinosa (lamina II) neurons in the dorsal horn. The data demonstrate that isoflurane modulates synaptic transmission from peripheral to the spinal cord via both pre- and postsynaptic effects and these actions may underlie its spinal anesthesia.

The perfusion index (PI), calculated from the photoplethysmographic waveform, reflects peripheral vasomotor tone. As such, the PI serves as a surrogate for quantitative measures of drug-induced vasoconstriction or vasodilation. This study aimed to compare the effect on the PI of desflurane and sevoflurane at equi-anaesthetic concentrations in patients undergoing single-agent inhalation anaesthesia, where equi-anaesthetic dose was based on the known minimum alveolar concentration of these agents.We randomly allocated patients scheduled for arthroscopic knee surgery to receive either desflurane or sevoflurane general anaesthesia after target-controlled induction of anaesthesia with propofol. Anaesthesia was maintained at age-corrected minimum alveolar concentration 1.0, under neuromuscular block (rocuronium). The PI and haemodynamic data were recorded every minute for 35 min after induction of anaesthesia and after standardised nociceptive stimulation. The primary outcome was PI, compared between the groups over time (repeated-measures analysis of variance). Secondary outcomes included MAP and HR.Sixty-nine participants (mean [range] age: 42 yr [19-65 yr]; 49% females) were assigned to either desflurane (n=34) or sevoflurane (n=35). The PI remained higher under desflurane compared with sevoflurane, both before (mean difference [MD]: 3.3; 95% confidence intervals [CIs]: 2.0-4.7; P0.001) and after tetanic stimulation (MD: 2.8; 95% CI: 2.0-3.7; P0.001). Higher PI paralleled lower MAP in participants assigned to desflurane anaesthesia (P0.001), both before (MD: 8 mm Hg; 95% CI: 4-12) and after nociceptive stimulation (MD: 14 mm Hg; 95% CI: 7-22). HR was similar throughout.These findings suggest that at equipotent doses, desflurane exerts more potent vasodilatory properties and lowers blood pressure by a magnitude potentially associated with harm.NCT03570164.

OBJECTIVE To determine the minimum alveolar concentration (MAC) of isoflurane in donkeys and characterize recovery from anesthesia. ANIMALS 7 healthy castrated male adult donkeys. PROCEDURES Anesthesia was induced with propofol and maintained under mechanical ventilation with 1.3% isoflurane end-tidal concentration (ETiso). The MAC of isoflurane was determined after a 60-minute propofol washout period using the bracketing method. A continuous noxious electrical stimulation was applied to the oral mucosa for 1 minute or until the donkey moved. The ETiso was increased or decreased by 10% depending on the response, and MAC was defined as the average of 2 ETiso values allowing and preventing movement in response to stimulation. Arterial blood gases were measured during anesthesia and the recovery period. Unassisted recovery was timed, and a quality score was assigned from 1 (very poor) to 5 (excellent). RESULTS The mean dose of propofol required for induction was 3.0 ± 0.6 mg/kg. The MAC of isoflurane was 1.44 ± 0.13%. One donkey was excluded from the study because it was still responsive when stimulated at ETiso of 2.8%. Immediately after extubation, the median (range) partial pressure of oxygen in the arterial blood was 63 (minimum to maximum, 46 to 72) mm Hg and 3 donkeys were hypoxemic (partial pressure of arterial oxygen < 60 mm Hg). The median time to standing was 13 (7 to 38) minutes, while the recovery score was 3 (2 to 5). CLINICAL RELEVANCE The MAC of isoflurane in donkeys is similar to that reported in other species. Oxygen support should be provided to donkeys during recovery from isoflurane anesthesia to prevent hypoxemia.

What is known and objective Low-dose ketamine can reduce the minimum alveolar concentration of sevoflurane necessary to block the adrenergic response (MACBAR ) in animals. However, the effects of low-dose ketamine on the sevoflurane MACBAR in patients undergoing laparoscopic surgery are unclear. The aim of this study was to investigate the effects of three different low doses of ketamine on the MACBAR of sevoflurane in patients undergoing laparoscopic cholecystectomy. Methods One hundred patients who underwent laparoscopic cholecystectomy were enrolled. After general anaesthesia induction and tracheal intubation, patients received sevoflurane anaesthesia in combination with a loading dose of saline followed by infusion or a loading dose of 0.5 mg/kg ketamine followed by a continuous infusion of 5 (K1 group), 10 (K2 group) and 20 μg/kg/min (K3 group). The target concentration of end-tidal sevoflurane was maintained for at least 20 minutes before carbon dioxide pneumoperitoneum stimulus. The MACBAR of sevoflurane in each group was determined by using an up-and-down sequential allocation technique. Results and discussion Seventy-one patients completed the study. The values of MACBAR for sevoflurane were 5.3% in the K0 , 4.8% in K1 , 3.3% in K2 and 3.2% in K3 groups. The use of ketamine significantly reduced the MACBAR of sevoflurane compared to sevoflurane alone. The K2 and K3 groups showed significantly lower values of MACBAR than that in the K1 group. However, a higher dose of ketamine in the K3 group did not further reduce the sevoflurane MACBAR . The mean arterial blood pressure (MAP) values before pneumoperitoneum in the K2 and the K3 groups were significantly higher compared to those in the K0 and K1 groups. Compared with the values before pneumoperitoneum, the heart rate and MAP after pneumoperitoneum were significantly increased. Overall, the haemodynamics remained stable during the study period in all groups. What is new and conclusion A loading dose of 0.5 mg/kg ketamine followed by a continuous infusion of 10.0 μg/kg/min led to a significant decrease in the MACBAR of sevoflurane in patients undergoing laparoscopic cholecystectomy.

Objectives: In this study, we aimed to evaluate the effects of isoflurane and sevoflurane on cerebral ischemia in patients undergoing intracranial tumour surgery by measuring protein S-100B in serum. Patients undergoing intracranial surgery are at risk for cerebral ischemia. The presence of S100-B in serum is an early and the most sensitive determinant of cerebral ischemia. Methods: Twenty patients, scheduled for elective, intracranial tumor surgery were enrolled in this prospective and randomized study. Anaesthesia induction was performed with thiopental, fentanyl and vecuronium. In the maintenance, isoflurane or sevoflurane was administered in a minimum alveolar concentration of 0.8-1.2%. Peripheral blood samples were taken at 9 different times to measure protein S-100B levels. Results: Demographic data, heart rate, systolic arterial pressure, mean arterial pressure and the deviations in the end-tidal carbon dioxide were similar in the study groups (p > 0.05), whereas diastolic arterial pressure was found to be significantly decreased in isoflurane group after the intubation, and there was an increase in the sevoflurane group (p < 0.05). Also there was no significant difference between the groups regarding protein S-100B levels. Conclusions: It was concluded that isoflurane and sevoflurane have similar neuroprotective effects against cerebral ischemia and sevoflurane may be a good alternative to isoflurane.

Background Cannabis has increasingly been used for medical and recreational purposes. The main pharmacological compound in cannabis is tetrahydrocannabinol (THC), which has sedative, anxiolytic and analgesic effects. In some animal models, THC has also been shown to reduce the minimum alveolar concentration (MAC) of halothane and cyclopropane, but its effect on sevoflurane, currently the most commonly used inhalational anaesthetic agent, has not been investigated. Objective To investigate the effect of THC on the MAC of sevoflurane in rats. Methods Observer-blinded, randomised controlled trial. Setting Centre for Biomedical Research of the Medical University of Vienna, 2019. Individuals Thirty-eight adult Wistar rats. Interventions The rats were allocated randomly into one of two groups. Group A received THC 10 mg kg and group B received the corresponding volume of placebo via gastric gavage (administration through a tube placed in the distal oesophagus). The rats were then individually anaesthetised in an airtight sevoflurane-flooded chamber, and the MAC in both groups was determined using Dixon's up-and-down method. Blood samples were drawn to measure serum concentrations of THC. Main outcome measures The primary outcome was the MAC of sevoflurane in Groups A and B. Results The bootstrap estimate of the MAC of sevoflurane was 2.1 (95% confidence interval 1.8 to 2.4) vol% in the THC group and 2.8 (95% confidence interval 2.7 to 2.9) vol% in the placebo group, corresponding to a significant MAC reduction of 26% in response to THC. Conclusion Gastric administration of THC 10 mg kg significantly reduced the MAC of sevoflurane by 26%. Trial registration Not applicable.

Background Volatile anesthetics moderately depress respiratory function at clinically relevant concentrations. Phox2b-expressing chemosensitive neurons in the retrotrapezoid nucleus, a respiratory control center, are activated by isoflurane, but the underlying mechanisms remain unclear. The hypothesis of this study was that the sodium leak channel contributes to the volatile anesthetics-induced modulation of retrotrapezoid nucleus neurons and to respiratory output. Methods The contribution of sodium leak channels to isoflurane-, sevoflurane-, and propofol-evoked activity of Phox2b-expressing retrotrapezoid nucleus neurons and respiratory output were evaluated in wild-type and genetically modified mice lacking sodium leak channels (both sexes). Patch-clamp recordings were performed in acute brain slices. Whole-body plethysmography was used to measure the respiratory activity. Results Isoflurane at 0.42 to 0.50 mM (~1.5 minimum alveolar concentration) increased the sodium leak channel–mediated holding currents and conductance from −75.0 ± 12.9 to −130.1 ± 34.9 pA (mean ± SD, P = 0.002, n = 6) and 1.8 ± 0.5 to 3.6 ± 1.0 nS (P = 0.001, n = 6), respectively. At these concentrations, isoflurane increased activity of Phox2b-expressing retrotrapezoid nucleus neurons from 1.1 ± 0.2 to 2.8 ± 0.2 Hz (P < 0.001, n = 5), which was eliminated by bath application of gadolinium or genetic silencing of sodium leak channel. Genetic silencing of sodium leak channel in the retrotrapezoid nucleus resulted in a diminished ventilatory response to carbon dioxide in mice under control conditions and during isoflurane anesthesia. Sevoflurane produced an effect comparable to that of isoflurane, whereas propofol did not activate sodium leak channel–mediated holding conductance. Conclusions Isoflurane and sevoflurane increase neuronal excitability of chemosensitive retrotrapezoid nucleus neurons partly by enhancing sodium leak channel conductance. Sodium leak channel expression in the retrotrapezoid nucleus is required for the ventilatory response to carbon dioxide during anesthesia by isoflurane and sevoflurane, thus identifying sodium leak channel as a requisite determinant of respiratory output during anesthesia of volatile anesthetics. Editor’s Perspective What We Already Know about This Topic What This Article Tells Us That Is New

BACKGROUND Anesthetic regimens using dexmedetomidine and short-acting opioids have been suggested as potential alternatives to sevoflurane-based anesthesia in children. The primary aim of this study is to compare demographics, intraoperative characteristics, and complications of general anesthetics in which dexmedetomidine and opioids were used without sevoflurane, or in combination with a low sevoflurane concentration, in children 36 months old and younger. The secondary aim is to evaluate intraoperative bispectral index (BIS) values when available in these patients. METHODS General anesthetics performed between January 1, 2017, and May 1, 2018, in children 2 years and younger who received dexmedetomidine and remifentanil, with or without sevoflurane, were identified. Additional anesthetics performed during this time in children 36 months and younger who received dexmedetomidine and opioids and had BIS monitoring were also identified. Charts were reviewed for demographic and intraoperative variables, including drug administration and hemodynamic data. RESULTS A total of 244 patients were identified. All but 22 patients received remifentanil. Ninety-two patients received sevoflurane with a mean end-tidal concentration of 0.84% (SD 0.43). Compared to the sevoflurane group, the nonsevoflurane group received more remifentanil (median dose 0.4 μg/kg/min vs 0.2 μg/kg/min, difference of 0.1 μg/kg/min, 95% CI 0.1-0.3, P

Objective To evaluate the effects of constant rate infusions (CRIs) of dexmedetomidine and remifentanil alone and their combination on minimum alveolar concentration (MAC) of sevoflurane in dogs. Study design Randomized crossover experimental study. Animals A total of six (three males, three females) healthy, adult neutered Beagle dogs weighing 12.6 ± 1.4 kg. Methods Anesthesia was induced with sevoflurane in oxygen until endotracheal intubation was possible and anesthesia maintained with sevoflurane using positive-pressure ventilation. Each dog was anesthetized five times and was administered each of the following treatments: saline (1 mL kg–1 hour–1) or dexmedetomidine at 0.1, 0.5, 1.0 or 5.0 μg kg–1 loading dose intravenously over 10 minutes followed by CRI at 0.1, 0.5, 1.0 or 5.0 μg kg–1 hour–1, respectively. Following 60 minutes of CRI, sevoflurane MAC was determined in duplicate using an electrical stimulus (50 V, 50 Hz, 10 ms). Then, CRI of successively increasing doses of remifentanil (0.15, 0.60 and 2.40 μg kg–1 minute–1) was added to each treatment. MAC was also determined after 30 minutes equilibration at each remifentanil dose. Isobolographic analysis determined interaction from the predicted doses required for a 50% MAC reduction (ED50) with remifentanil, dexmedetomidine and remifentanil combined with dexmedetomidine, with the exception of dexmedetomidine 5.0 μg kg–1 hour–1, obtained using log-linear regression analysis. Results The sevoflurane MAC decreased dose-dependently with increasing infusion rates of dexmedetomidine and remifentanil. Remifentanil ED50 values were lower when combined with dexmedetomidine than those obtained during saline–remifentanil. Synergistic interactions between dexmedetomidine and remifentanil for MAC reduction occurred with dexmedetomidine at 0.5 and 1.0 μg kg–1 hour–1. Conclusions and clinical relevance Combined CRIs of dexmedetomidine and remifentanil synergistically resulted in sevoflurane MAC reduction. The combination of dexmedetomidine and remifentanil effectively reduced the requirement of sevoflurane during anesthesia in dogs.

In low‐flow anesthesia (LFA), there is a wash‐in period in which usually high fresh gas flow (FGF) rates are used to achieve the required initial concentration of anesthetic agent in the alveoli. The aim of this study was to compare the efficiency, safety and the consumption of desflurane in LFA using constant FGF (1 L/min) and conventional LFA using high FGF (4 L/min) during the wash‐in period. Eighty patients, who were scheduled for elective surgery under general anesthesia with endotracheal intubation, were enrolled in the study. Wash‐in was accomplished with 1 L/min FGF (50% O2, 50% air) and 18% desflurane in group 1; and by 4 L/min FGF (50% O2, 50% air) and 6% desflurane in group 2. Throughout the surgery, the vaporizer was adjusted to maintain 0.6 to 0.8 minimum alveolar concentration (MAC). The time required to reach 0.7 MAC was shorter in group 1 (160 seconds [135‐181] vs 288 seconds [240‐500], P

Background Investigations of the electrophysiology of gaseous anesthetics xenon and nitrous oxide are limited revealing inconsistent frequency-dependent alterations in spectral power and functional connectivity. Here, the authors describe the effects of sedative, equivalent, stepwise levels of xenon and nitrous oxide administration on oscillatory source power using a crossover design to investigate shared and disparate mechanisms of gaseous xenon and nitrous oxide anesthesia. Methods Twenty-one healthy males underwent simultaneous magnetoencephalography and electroencephalography recordings. In separate sessions, sedative, equivalent subanesthetic doses of gaseous anesthetic agents nitrous oxide and xenon (0.25, 0.50, and 0.75 equivalent minimum alveolar concentration–awake [MACawake]) and 1.30 MACawake xenon (for loss of responsiveness) were administered. Source power in various frequency bands were computed and statistically assessed relative to a conscious/pre-gas baseline. Results Observed changes in spectral-band power (P < 0.005) were found to depend not only on the gas delivered, but also on the recording modality. While xenon was found to increase low-frequency band power only at loss of responsiveness in both source-reconstructed magnetoencephalographic (delta, 208.3%, 95% CI [135.7, 281.0%]; theta, 107.4%, 95% CI [63.5, 151.4%]) and electroencephalographic recordings (delta, 260.3%, 95% CI [225.7, 294.9%]; theta, 116.3%, 95% CI [72.6, 160.0%]), nitrous oxide only produced significant magnetoencephalographic high-frequency band increases (low gamma, 46.3%, 95% CI [34.6, 57.9%]; high gamma, 45.7%, 95% CI [34.5, 56.8%]). Nitrous oxide—not xenon—produced consistent topologic (frontal) magnetoencephalographic reductions in alpha power at 0.75 MACawake doses (44.4%; 95% CI [−50.1, −38.6%]), whereas electroencephalographically nitrous oxide produced maximal reductions in alpha power at submaximal levels (0.50 MACawake, −44.0%; 95% CI [−48.1,−40.0%]). Conclusions Electromagnetic source-level imaging revealed widespread power changes in xenon and nitrous oxide anesthesia, but failed to reveal clear universal features of action for these two gaseous anesthetics. Magnetoencephalographic and electroencephalographic power changes showed notable differences which will need to be taken into account to ensure the accurate monitoring of brain state during anaesthesia. Editor’s Perspective What We Already Know about This Topic What This Article Tells Us That Is New

Both standard and sustained-release injectable formulations of buprenorphine (Bup and BupSR, respectively) are used as preemptive analgesics, potentially affecting gas anesthetic requirements. This study tested the effects of Bup and BupSR on isoflurane requirements and confirmed that buprenorphine could reduce isoflurane requirements during a laparotomy in mice. We hypothesized that both Bup and BupSR would significantly decrease the required minimum alveolar concentration (MAC) of isoflurane. C57BL/6 mice received either isotonic crystalloid fluid (control), Bup (0.1 mg/kg), or BupSR (1.2 mg/kg) subcutaneously 10 min prior to the induction of anesthesia. Each anesthetized mouse was tested at 2 isoflurane concentrations. A 300-g noxious stimulus was applied at each isoflurane concentration, alternating between hindfeet. In addition, a subset of mice underwent terminal laparotomy or 60 min of anesthesia after injection with Bup, BupSR, or saline to ensure an appropriate surgical plane of anesthesia. Mice were maintained at the lowest isoflurane concentration that resulted in 100% of mice at a surgical plane from the aforementioned MAC experiments (control, 2.0%; Bup and BupSR, 1.7%). Analysis showed that both Bup and BupSR significantly decreased isoflurane requirements by 25.5% and 14.4%, respectively. The isoflurane MAC for the control injection was 1.80% ± 0.09%; whereas Bup and BupSR decreased MAC to 1.34% ± 0.08% and 1.54% ± 0.09%, respectively. Sex was not a significantly different between the injection groups during MAC determination. All of the mice that underwent surgery achieved a surgical plane of anesthesia on the prescribed regimen and recovered normally after discontinuation of isoflurane. Lastly, heart and respiratory rates did not differ between mice that underwent surgery and those that were anesthetized only. Bup and BupSR are MAC-sparing in male and female C57BL/6 mice and can be used for effective multimodal anesthesia.

Objective To determine the pharmacokinetics of dopamine following a short infusion in isoflurane-anesthetized rabbits. Study design Prospective, descriptive pharmacokinetic study. Animals A group of six adult female New Zealand White rabbits weighing 4.4 ± 0.2 kg. Methods Rabbits were anesthetized with isoflurane in oxygen and maintained at 1.2 × minimum alveolar concentration of isoflurane (2.3% atmosphere). Dopamine (30 μg kg–1 minute–1) was infused for 10 minutes. Arterial blood was sampled prior, during and following the infusion at various intervals for 1 hour. Results A one-compartment model with baseline concentration best fitted the time–plasma dopamine concentration data. Estimated typical population value (interindividual variability) for volume of distribution and clearance were 10.3 (232%) L kg–1 and 9.9 (508%) L minute–1 kg–1, respectively. Conclusions and clinical relevance There was a large degree of interindividual variation in the disposition of dopamine. The large volume of distribution and high metabolic clearance rate reported for dopamine in this study likely explains the lack of clinical efficacy of dopamine in rabbits at doses up to 30 μg kg–1 minute–1.

Minimizing sympathetic stimulation under anesthesia prevents activation of the neuroendocrine stress response. The minimum alveolar concentration blunting adrenergic responses in 50% of the population when exposed to a noxious stimulus is defined as MAC-BAR. The purpose of this study was to determine the MAC-BAR of sevoflurane (MAC-BARsevo) in sheep and the MAC-BAR sparing effects of ketamine. Thirteen healthy Dorset-cross adult ewes, 4 ± 1 year old and weighing 74 ± 9 kg, were enrolled in a randomized blinded crossover study design. Ewes were anesthetized twice for MAC-BARsevo determination. After face mask induction with sevoflurane, sheep received intravenous ketamine at 1.5 mg/kg and a constant rate infusion of 1.5 mg/kg/h or an equivalent volume of saline (placebo). After 8 day washout, the other treatment was administered. A bracketing technique was used for MAC-BARsevo determination and values were collected in duplicate. The mechanical stimulus (sponge forceps) was applied at the coronary band for 1 min and blood was collected for ketamine plasma concentrations. The MAC-BARsevo values of each treatment were compared using a paired t-test. Mean MAC-BARsevo of the ketamine and placebo were 2.73 ± 0.23% and 2.77 ± 0.31%, respectively and no significant difference was found (p = .638). Average ketamine plasma concentrations was 1.54 ± 0.18 μg/mL maintained through the study. Ketamine at 1.5 mg/kg, followed by 1.5 mg/kg/h, did not decrease the MAC-BARsevo in sheep. Further studies to determine the effect of higher doses of ketamine on inhalational anesthetic agents and their potential adverse effects are warranted.

Background and Aims: Minimum alveolar concentration (MAC) of inhalational agent denotes the requirement of it to maintain adequate plane of general anaesthesia. The precision to the maintenance of anaesthesia can be further guided by use of entropy to titrate the depth of anaesthesia. Regional anaesthesia and the concomitant deafferentation will decrease the need of general anaesthetics. We conducted a randomised double-blind trial to quantify the effect of addition of regional anaesthesia to sevoflurane based general anaesthesia technique guided by entropy to achieve satisfactory depth of anaesthesia. Methods: Forty patients posted for elective laparotomies were randomised to two groups. All patients received a bolus followed by an epidural infusion. Group GE (general anaesthesia + epidural bupivacaine) received 0.25% epidural bupivacaine and Group GS received epidural saline. Both groups received narcotic, relaxant and sevoflurane anaesthesia guided by entropy monitoring. The state entropy (SE) was maintained at 40–60 by titrating end tidal sevoflurane concentration (ETsevo). Heart rate, blood pressure, SpO2, end tidal carbon dioxide (ETCO2) and sevoflurane were recorded. Results: Both groups were similar in heart rate and mean blood pressure during anaesthesia maintenance. The minimum ETSevo required to maintain entropy between 40 and 60 in group GE was 0.53% compared to 0.95% in group GS the epidural saline group (P < 0.001). The end-tidal sevoflurane requirement to maintain adequate depth of anaesthesia dropped by 44.2% in group GE. Conclusion: Lower concentrations of volatile anaesthetic are required when entropy-guided general anaesthesia is combined with regional blockade.

Background: Robotic and minimal invasive surgeries pose challenges to the anaesthesiologists. Dexmedetomidine (dexmed), with distinct properties of sedation and analgesia has emerged as a promising drug. Our primary aim, in this double-blinded study, was to evaluate reduction in the intraoperative opioid requirement with the use of intravenous dexmed infusion. Secondary objectives included effect on intraoperative anaesthetic and postoperative analgesic requirement. Methodology: After approval from Ethics board and registration of the trial, 46 eligible patients planned for robotic oncosurgeries (abdomen) were included. As per computer generated randomisation chart, patients were randomised into either dexmed or saline group. Five minutes after insufflation of the abdomen, the study drug bolus—saline or dexmed (1 μg/kg) was given over 10 min and was followed by maintenance infusion (0.2 μg/kg/h) until release of pneumoperitoneum. Study drug titration, fentanyl boluses, and changes in minimum alveolar concentration (MAC) of inhalational agent were protocolised. Results: The mean intraoperative fentanyl requirement was significantly lower in the dexmed group 192.6 μg (±66.4) versus the saline group 260.7 μg (±88.6), P = 0.013. The MAC requirement of inhalational agent was significantly lower in the dexmed group. Intraoperative episodes of hypotension and bradycardia were similar in both groups. First analgesic request, 24 h postoperative pain scores and side effects profile were comparable in both groups. Conclusion: Intraoperative dexmed (bolus of 1 μg/kg followed by 0.2 μg/kg/h infusion) has an opioid and inhalational anaesthetic sparing role during robotic oncosurgeries. However, no benefit of the infusion is seen in the postoperative period.

CO2 has anesthetic potency and effectively influences the circulatory system. We investigated the effects of Etco2 on the minimum alveolar concentration of sevoflurane that blunts the adrenergic response to surgical incision (MAC-BAR) in patients undergoing radical surgery for gastric carcinoma.Ninety patients undergoing radical gastric-carcinoma surgery under general anesthesia were enrolled and randomly assigned into 3 groups. After intubation, the Etco2 in group L (n = 30), group N (n = 30), and group H (n = 30) was adjusted to 25 mm Hg ≤ Etco230 mm Hg, 30 mm Hg ≤ Etco240 mm Hg, and 40 mm Hg ≤ Etco245 mm Hg, respectively, by changes in controlled ventilation. Hemodynamics and depth of anesthesia were observed before and after skin incision. The MAC-BAR of sevoflurane for each group was determined using an up-and-down sequential-allocation technique.To obtain 7 crossovers, 25, 26, and 26 patients were used in group L, group N, and group H, respectively. The MAC-BAR of sevoflurane using the up-and-down method for group H was significantly lower than that for group L (2.3% [95% confidence interval {CI}, 2.2-2.4] vs 2.9% [95% CI, 2.7-3.0]; difference, -0.6% [95% CI, -0.7 to -0.4], P.001) and group N (2.3% [95% CI, 2.2-2.4] vs 2.8% [95% CI, 2.8-2.9]; difference, -0.5% [95% CI, -0.7 to -0.4], P.001), while no significant difference was found between group L and group N (P = 1.000).Higher Etco2 levels (Etco2 values equal to 40 mm Hg or higher) can effectively decrease the MAC-BAR of sevoflurane in patients undergoing radical surgery for gastric carcinoma.

ObjectivePhase-amplitude coupling between high-frequency (≥150 Hz) and delta (3-4 Hz) oscillations - modulation index (MI) - is a promising, objective biomarker of epileptogenicity. We determined whether sevoflurane anesthesia preferentially enhances this metric within the epileptogenic zone.MethodsThis is an observational study of intraoperative electrocorticography data from 621 electrodes chronically implanted into eight patients with drug-resistant, focal epilepsy. All patients were anesthetized with sevoflurane during resective surgery, which subsequently resulted in seizure control. We classified ‘removed’ and ‘retained’ brain sites as epileptogenic and non-epileptogenic, respectively. Mixed model analysis determined which anesthetic stage optimized MI-based classification of epileptogenic sites.ResultsMI increased as a function of anesthetic stage, ranging from baseline (i.e., oxygen alone) to 2 minimum alveolar concentration (MAC) of sevoflurane, preferentially at sites showing higher initial MI values. This phenomenon was accentuated just prior to sevoflurane reaching 2 MAC, at which time, the odds of a site being classified as epileptogenic were enhanced by 86.6 times for every increase of 1 MI.ConclusionsIntraoperative MI best localized the epileptogenic zone immediately before sevoflurane reaching 2 MAC in this small cohort of patients.SignificanceProspective, large cohort studies are warranted to determine whether sevoflurane anesthesia can reduce the need for extraoperative, invasive evaluation.Highlights-We measured the modulation index on intraoperative electrocorticography recording.-Sevoflurane enhanced the modulation index differentially across the epileptogenic and non- epileptogenic sites.-The modulation index best discriminated these two groups of sites before sevoflurane reached 2 minimum alveolar concentration.

Background Better protection can be provided during neurosurgery due to the establishment of somatosensory-evoked potential (SEP) and motor-evoked potential (MEP) monitoring technologies. However, some studies have showed that inhaled halogenated anesthetics have a significant impact on neurophysiological monitoring. Methods A total of 40 consecutive patients undergoing neurosurgery were randomly assigned to two groups receiving inhaled anesthetics, either desflurane or sevoflurane. Multiples levels (concentrations of 0.3, 0.6 and 0.9) of anesthetics were administered at minimum alveolar concentration (MAC), and then the latencies and amplitudes of SEPs and MEPs were recorded. Results SEP and MEP signals were well preserved in patients who underwent neurosurgery under general anesthesia supplemented with desflurane or sevoflurane at concentrations of 0.3, 0.6 and 0.9 MAC. In each desflurane or sevoflurane group, the amplitudes of SEPs and MEPs decreased and the latencies of SEPs were prolonged significantly as the MAC increased (P P P Conclusions SEPs and MEPs were inhibited in a dose-dependent manner by both desflurane and sevoflurane. At the same MAC concentration, desflurane appeared to have a stronger inhibitory effect than sevoflurane. All patients studied had normal neurological examination findings, hence, these results may not be applicable to patients with preexisting deficits. Trial registration The study registered on the Chinese Clinical Trial Registry (www.chictr.org.cn), Clinical Trials identifier ChiCTR2100045504 (18/04/2021).

To determine the effect of butorphanol, administered by intravenous (IV) infusion, on the minimum alveolar concentration of isoflurane (MACRandomized, placebo-controlled, crossover experimental study.A group of six healthy adult male neutered cats.Cats were anesthetized with isoflurane in oxygen. A venous catheter was placed for fluid and drug administration, and an arterial catheter was placed for measurement of arterial pressure and blood sampling. Four treatments were administered at random with at least 2 week interval between treatments: saline (control), butorphanol low dosage (treatment LD; 0.25 mg kgButorphanol reduced MACButorphanol caused a dosage-dependent MAC

BACKGROUND Intraoperative flash visual evoked potential (FVEP) can be used to monitor visual function during spine surgery. However, it is limited due to the previous perception of its sensitivity to inhalation anesthesia. We conducted this trial to test the noninferiority of sevoflurane-propofol-balanced anesthesia (BA) versus popular propofol-based total intravenous anesthesia (TIVA) on the amplitude of FVEP during spine surgery. METHODS A total of 60 patients undergoing spine surgery were randomized to receive either sevoflurane-propofol-balanced anesthesia (BA group) or propofol-based total intravenous anesthesia (TIVA group) for anesthesia maintenance. We titrated the propofol plasma concentration to keep the bispectral index (BIS) values between 40 and 50. The primary outcome was the P100-N145 amplitudes of FVEP at 120 minutes after induction of anesthesia. The noninferiority margin (δ) was defined as 10% of the P100-N145 amplitude at 120 minutes after induction in the TIVA group. If the confidence interval (CI) for mean differences of P100-N145 amplitude at 120 minutes after induction between BA and TIVA groups lied above the lower limit of -δ with P < .025, we defined BA group was noninferior to TIVA group. RESULTS Fifty-nine patients were included in the final analysis. The amplitude of P100-N145 at 120 minutes after anesthesia induction in group BA was noninferior to group TIVA (3.8 [1.3] µV vs 3.2 [1.6] µV, -δ = -0.32, mean difference, 0.57, 95% CI, -0.18 to 1.33, P for noninferiority = .015). CONCLUSIONS The effect of 0.5 minimum alveolar concentration (MAC) of sevoflurane-propofol-balanced anesthesia on the P100-N145 amplitude of FVEP was noninferior to that of propofol-based TIVA under comparable BIS range.

The solubility of inhalational anaesthetics in the bloodstream is related to the minimum alveolar concentration (MAC), which is an indicator of anaesthetic gas potency. The blood-gas partition coefficient (Kbg) is a measure of how much anaesthetics bind to plasma proteins in the blood compared to air. Just like the octanol–water partition coefficient, the Kbg may be related to the molecular dipole moment (μ), which can be modulated by the molecular conformation. Our quantum-chemical calculations demonstrated that subtle stereoelectronic interactions, namely those responsible for the anomeric and gauche effects, control the conformational equilibrium of some widely used volatile fluorinated anaesthetics and, consequently, of their molecular dipole moments. Since a remarkable correlation between empirical Kbg and calculated μ was found for these anaesthetics, the average molecular dipole moments may be used to predict the anaesthetic gas potency and other properties, such as lipid solubility, of inhalational anaesthetic analogs.

Objective: While clinical use of sevoflurane has been increasing in veterinary medicine, this anaesthetic can cause dose-dependent hypotension, hypoventilation, impaired cardiac contractility, and hypothermia. Because of these side effects, sevoflurane must be carefully titrated and vigilantly monitored to avoid excessive anaesthetic depth. One of the anaesthetic depth evaluation using a minimum alveolar concentration (MAC) has been defined as “produces immobility in 50% of animals exposed to noxious stimulus.” Limited information regarding the MAC of sevoflurane required for blunting adrenergic responses (MAC-BAR) in cats currently exists. Therefore, this study was designed to compare the MAC and MAC-BAR of sevoflurane required to prevent autonomic responses and purposeful movements in cats. Methods: Six adult healthy domestic short haired cats (1year old, 3 males and 3 females) were anaesthetized with sevoflurane on two occasions with a minimum 14-day washout period to determine sevoflurane MAC and MACBAR. Results: The difference between sevoflurane MAC (2.92 ±0.47%) and MAC-BAR (3.24 ± 0.41%) was not statistically significant. Conclusions and Clinical Relevance: These results suggested that the detrimental cardiovascular side effects such as hypotension and impaired cardiac contractility can easily occur in sevoflurane-anaesthetized cats.

BACKGROUND: Recent studies point to a fundamental distinction between population-based and individual-based anaesthetic pharmacology. At the population level, anaesthetic potency is defined as the relationship between drug concentration and the likelihood of response to a stimulus. At the individual level, even when the anaesthetic concentration is held constant, fluctuations between the responsive and unresponsive states are observed. Notably, these spontaneous fluctuations exhibit resistance to state transitions R(st). Therefore, the response probability in each individual depends not just upon the drug concentration, but also upon responses to previous stimuli. Here, we hypothesise that R(st) is distinct from drug potency and is differentially modulated by different anaesthetics. METHODS: Adult (14–24 weeks old) C57BL/6J male mice (n=60) were subjected to repeated righting reflex (RR) assays at equipotent steady-state concentrations of isoflurane (0.6 vol%), sevoflurane (1.0 vol%), and halothane (0.4 vol%). RESULTS: Fluctuations in RR were observed for all tested anaesthetics. Analysis of these fluctuations revealed that R(st) was differentially modulated by different anaesthetics (F[2, 56.01]=49.59; P

Objective To characterize the cardiopulmonary effects of dexmedetomidine, with or without vatinoxan, in isoflurane-anesthetized cats. Study design Randomized, crossover experimental study. Animals A group of six adult healthy male neutered cats. Methods Cats were instrumented during anesthesia with isoflurane in oxygen. Isoflurane end-tidal concentration was set to 1.25 minimum alveolar concentration (MAC). Dexmedetomidine was administered using a target-controlled infusion system to achieve and maintain 10 target plasma concentrations ranging from 0 to 40 ng mL–1. Furthermore, vatinoxan or an equivalent volume of saline was administered using a target-controlled infusion system to achieve and maintain a target plasma concentration of 4 μg mL–1. Isoflurane concentration was adjusted after each change in dexmedetomidine concentration to maintain a concentration equivalent to 1.25 MAC. Heart rate (HR), arterial blood pressure, central venous pressure (CVP), pulmonary artery pressure (PAP), pulmonary artery occlusion pressure (PAOP), body temperature, cardiac output, arterial and mixed-venous blood gas and pH and drug concentrations were measured. Additional variables were calculated from the measurements. Results Dexmedetomidine alone resulted in decreased HR, cardiac index, stroke index and oxygen delivery, and increased systolic, mean (MAP) and diastolic arterial pressure, CVP, PAP, PAOP, systemic vascular resistance index, rate-pressure product, left ventricular stroke work index and oxygen extraction ratio. Vatinoxan resulted in severe hypotension at target plasma dexmedetomidine concentrations Conclusions and clinical relevance Vatinoxan, at the plasma concentration maintained in this study, attenuated the cardiovascular effects of dexmedetomidine in isoflurane-anesthetized cats. However, its administration resulted in hypotension, which may limit its clinical usefulness.

Objective To characterize the effect of α2-adrenoceptor antagonism on the minimum alveolar concentration of isoflurane (MACISO) in cats. Study design Prospective experimental study. Animals A group of five healthy adult male neutered cats. Methods Cats were anesthetized with isoflurane in oxygen and instrumented. MACISO was determined in duplicate in five cats, before and during administration of atipamezole (250 μg kg−1 followed by 250 μg kg−1 hour−1) using the bracketing technique and tail clamping. Estimates of MACISO obtained before and during administration of atipamezole were compared using a two-tailed paired t test. Results MACISO during atipamezole administration (mean ± standard deviation 2.73% ± 0.07%) was significantly larger than before atipamezole administration (1.95% ± 0.13%; p Conclusion and clinical relevance The role of α2-adrenoceptors in inhaled anesthetic-induced immobility may be larger than previously thought. Antagonism of an α2-adrenoceptor agonist during inhalation anesthesia may result in an increase in MAC disproportionate to the MAC reduction induced by the agonist.

Background Minimum alveolar concentration (MAC) and MAC-awake decrease with age. We hypothesised that, in clinical practice, (i) end-tidal MAC fraction in older patients would decline by less than the predicted age-dependent MAC decrease (i.e. older patients would receive relatively excessive anaesthetic concentrations), and (ii) bispectral index (BIS) values would therefore be lower in older patients. Methods We examined the relationship between end-tidal MAC fraction, BIS values, and age in 4699 patients > 30 yr in age at a single centre using unadjusted local regression (locally estimated scatterplot smoothing), Spearman's correlation, stratification, and robust univariable and multivariable linear regression. Results The end-tidal MAC fraction in older patients declined by 3.01% per decade (95% confidence interval [CI]: 2.56–3.45; P Conclusions The age-dependent decline in end-tidal MAC fraction delivered in clinical practice at our institution was less than the age-dependent percentage decrease in MAC and MAC-awake determined from published studies. Despite receiving higher aaMAC fractions, older patients paradoxically showed higher BIS values. This most likely suggests that the BIS algorithm is inaccurate in older adults.

Study objective To evaluate the intraoperative hemodynamics and medication requirements of cocaine-positive patients compared to matched cocaine-negative controls. Design Retrospective cohort study. Setting Public county hospital. Patients 821 patients undergoing general anesthesia. Measurements Incidence of hemodynamic events, defined by a mean arterial pressure of 105 mmHg or a heart rate of 100 beats per minute. Main results Cocaine-positive patients did not experience a higher incidence of hemodynamic events when compared with matched cocaine-negative patients. Cocaine-positive patients were not more likely to be administered vasopressors intraoperatively but did receive more anti-hypertensive agents. The minimum alveolar concentration of anesthetics used was similar between the two groups. Anesthesia duration, length of stay, and in-hospital mortality did not significantly differ between the two cohorts. Conclusions Cocaine-positive patients did not demonstrate more intraoperative hemodynamic events or adverse short-term outcomes as compared to matched cocaine-negative controls.

Background Quick and complete recovery of cognitive function after general anesthesia is desirable, particularly for working-age patients. Desflurane is less likely to have long-term effects than older-generation inhalational anesthetics, however, its short-term effects have not been fully investigated. Our objective was to elucidate the short-term effects of desflurane exposure on learning and memory in young adult rats. Methods Seven-week old male Sprague–Dawley rats were exposed to air (control), or desflurane at 0.7 or 1.2 minimum alveolar concentration (MAC) for 2 h (day 0). The inhibitory avoidance (IA) test was performed on day 1 to delineate the effects on contextual learning. Separate groups of control and 1.2 MAC desflurane animals underwent the IA test on days 3 and 7 to examine the time-dependent changes. Because the IA test is known to be dependent on the long-term potentiation (LTP) of the hippocampus and the trafficking of the GluR1 subunit of the α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor into the synapses, the effects of 1.2 MAC desflurane on these phenomena were evaluated on day 1. Results Desflurane at 1.2 MAC, but not 0.7 MAC, significantly decreased the IA latencies on day 1 compared with the control (one-way ANOVA, F [2,48] = 5.974, P = 0.005, post hoc Tukey’s, mean difference [95% confidence interval], control vs. 1.2 MAC, 168 [49.9 to 287], P = 0.004; control vs. 0.7 MAC, 67.5 [− 51.2 to 186], P = 0.362). The latencies were not affected on days 3 and 7 (day 3, control vs. desflurane, P = 0.861; day 7, control vs. desflurane, P > 0.999). Consistently, hippocampal LTP on day 1 was significantly suppressed in the desflurane group compared with the control group (P = 0.006). Moreover, immunoblotting analysis of synaptic GluR1 expression revealed that desflurane exposure significantly suppressed GluR1 delivery to the synapses after IA training. Conclusion Exposure to a relatively high concentration of desflurane caused reversible learning and memory impairment in young adult rats associated with suppression of GluR1 delivery to the synapses in the hippocampus.

The drug-induced, reversible coma of anaesthesia requires three clinical outcomes: unconsciousness, immobility, and the control of autonomic nervous system (ANS) responses to surgical stimulation. Producing the anaesthetised state with a single anaesthetic agent, such as an inhaled vapour or propofol, is challenging, primarily because suppressing ANS responses requires very high anaesthetic concentrations, resulting in haemodynamic depression and prolonged recovery. The antinociceptive effects of opioids (i.e. minimum alveolar concentration reduction) are thus central to the well-entrenched ‘balanced anaesthesia' concept. In recent years, the notion of ‘multimodal general anaesthesia' has extended the concept of balanced anaesthesia to include more drugs that target different neuroanatomical circuits and multiple neurophysiologic mechanisms. The opioid epidemic has provided some of the motivation to move away from opioids toward other adjunct drugs. Persistent opioid use after surgery is a component of the opioid epidemic and is a major concern for perioperative physicians. Potential solutions to the problem of persistent opioid use after surgery have focused on proper ‘opioid stewardship' after operation, wherein opioids are used conservatively in combination with other analgesic adjuncts, and excessive opioid prescribing for home use is avoided. But there is a paucity of data on how intraoperative opioid usage patterns may be contributing to persistent opioid use after surgery. There are cogent reasons to moderate perioperative opioid use, including intraoperative opioids, but whether these changes in practice integral to the multimodal general anaesthesia concept will improve anaesthesia outcomes, including persistent opioid use after surgery, is unknown. Studies investigating these issues are an important research priority.