The role of astrocytic γ-aminobutyric acid in the action of inhalational anesthetics.

BACKGROUND: Inhalational anesthetics target the inhibitory extrasynaptic γ-aminobutyric acid type A (GABAA) receptors. Both neuronal and glial GABA mediate tonic inhibition of the extrasynaptic GABAA receptors. However, the role of glial GABA during inhalational anesthesia remains unclear. This study aimed to evaluate whether astrocytic GABA contributes to the action of different inhalational anesthetics. METHODS: Gene knockout of monoamine oxidase B (MAOB) was used to reduce astrocytic GABA levels in mice. The hypnotic and immobilizing effects of isoflurane, sevoflurane, and desflurane were assessed by evaluating the loss of righting reflex (LORR) and tail-pinch withdrawal response (LTWR) in MAOB knockout and wild-type mice. Minimum alveolar concentration (MAC) for LORR, time to LORR, MAC for LTWR and time to LTWR of isoflurane, sevoflurane, and desflurane were assessed. RESULTS: Time to LORR and time to LTWR with isoflurane were significantly longer in MAOB knockout mice than in wild-type mice (P < 0.001 and P = 0.032, respectively). Time to LORR with 0.8 MAC of sevoflurane was significantly longer in MAOB knockout mice than in wild-type mice (P < 0.001), but not with 1.0 MAC of sevoflurane (P=0.217). MAC for LTWR was significantly higher in MAOB knockout mice exposed to sevoflurane (P < 0.001). With desflurane, MAOB knockout mice had a significantly higher MAC for LORR (P = 0.003) and higher MAC for LTWR (P < 0.001) than wild-type mice. CONCLUSIONS: MAOB knockout mice showed reduced sensitivity to the hypnotic and immobilizing effects of isoflurane, sevoflurane, and desflurane. Behavioral tests revealed that the hypnotic and immobilizing effects of inhalational anesthetics would be mediated by astrocytic GABA.

Desflurane improves electrical activity of neurons and alleviates oxygen-glucose deprivation-induced neuronal injury by activating the Kcna1-dependent Kv1.1 channel.

Several volatile anesthetics have presented neuroprotective functions in ischemic injury. This study investigates the effect of desflurane (Des) on neurons following oxygen-glucose deprivation (OGD) challenge and explores the underpinning mechanism. Mouse neurons HT22 were subjected to OGD, which significantly reduced cell viability, increased lactate dehydrogenase release, and promoted cell apoptosis. In addition, the OGD condition increased oxidative stress in HT22 cells, as manifested by increased ROS and MDA contents, decreased SOD activity and GSH/GSSG ratio, and reduced nuclear protein level of Nrf2. Notably, the oxidative stress and neuronal apoptosis were substantially blocked by Des treatment. Bioinformatics suggested potassium voltage-gated channel subfamily A member 1 (Kcna1) as a target of Des. Indeed, the Kcna1 expression in HT22 cells was decreased by OGD but restored by Des treatment. Artificial knockdown of Kcna1 negated the neuroprotective effects of Des. By upregulating Kcna1, Des activated the Kv1.1 channel, therefore enhancing K+ currents and inducing neuronal repolarization. Pharmacological inhibition of the Kv1.1 channel reversed the protective effects of Des against OGD-induced injury. Collectively, this study demonstrates that Des improves electrical activity of neurons and alleviates OGD-induced neuronal injury by activating the Kcna1-dependent Kv1.1 channel.

Comparison of the Effects of Desflurane and Sevoflurane on Variations in Salivary Melatonin and Sleep Disturbance After Total Knee Arthroplasty: A Single-center, Prospective, Randomized, Controlled, Open-label Study.

PURPOSE: Anesthesia has been shown to disrupt the circadian rhythm. Recovery of the circadian rhythm after general anesthesia might help alleviate symptoms of insomnia and postoperative delirium. We hypothesized that recovery of the circadian rhythm is faster after total knee arthroplasty (TKA) with desflurane than with sevoflurane. This study compared the influence of sevoflurane versus desflurane anesthesia on the postoperative circadian rhythm of melatonin in adults undergoing TKA. DESIGN: Single-center, prospective, randomized, controlled, open-label study. METHODS: This study involved adult patients undergoing TKA at a university hospital in Japan from May 1, 2018 to December 31, 2019. The primary outcome of the study was the comparison of the effect of sevoflurane and desflurane on the circadian rhythm of salivary melatonin for 3 days postoperatively. The secondary outcomes were postoperative fatigue and sleep quality for 3 days postoperatively. FINDINGS: Twenty-eight patients (American Society of Anesthesiologists physical status of I or II) were scheduled for TKA and randomized to receive sevoflurane (n = 14) or desflurane (n = 14) anesthesia. There was no significant difference in the melatonin concentration between the sevoflurane and desflurane groups. The salivary melatonin concentration after sevoflurane or desflurane anesthesia was significantly higher at 9:00 p.m. on a postoperative day (POD)0 and POD1 than on POD3 (P < .05). Patients in the desflurane group had significantly greater fatigue than those in the sevoflurane group at 7:00 a.m. and 12:00 p.m. on POD3 (P < .05). Patients in the sevoflurane group had a deeper sleep than those in the desflurane group on POD0 (P < .05). In the sevoflurane group, the sleep time during the night of POD2 was longer than that on POD0 (6.1 vs 4.2 hours, P < .05). CONCLUSIONS: Under the current study conditions, desflurane was equivalent to sevoflurane in terms of the postoperative salivary melatonin concentration and sleep disturbance after TKA but not in terms of recovering the postoperative circadian rhythm.

Effects of cerium oxide (CeO2) on liver tissue in liver ischemia-reperfusion injury in rats undergoing desflurane anesthesia.

INTRODUCTION: During liver surgery and transplantation, periods of partial or total vascular occlusion are inevitable and result in ischemia-reperfusion injury (IRI). Nanomedicine uses the latest technology, which has emerged with interdisciplinary effects, such as biomedical sciences, physics, and engineering, to protect and improve human health. Interdisciplinary research has brought along the introduction of antioxidant nanoparticles as potential therapeutics. The goal of this study was to investigate the effects of cerium oxide (CeO2) administration and desflurane anesthesia on liver tissue in liver IR injury. MATERIAL AND METHODS: Thirty rats were randomly divided into five groups: control (C), ischemia-reperfusion (IR), IR-desflurane (IRD), cerium oxide-ischemia reperfusion (CeO2-IR), and cerium oxide-ischemia reperfusion-desflurane (CeO2-IRD). In the IR, IRD, and CeO2-IRD groups, hepatic ischemia was induced after the porta hepatis was clamped for 120 min, followed by 120 min of reperfusion. Intraperitoneal 0.5 mg/kg CeO2 was administered to the CeO2 groups 30 min before ischemia. Desflurane (6%) was administered to the IRD and CeO2-IRD groups during IR. All groups were sacrificed under anesthesia. Liver tissue samples were examined under a light microscope by staining with hematoxylin-eosin (H&E). Malondialdehyde (MDA) levels, catalase (CAT), glutathione-s-transferase (GST), and arylesterase (ARE) enzyme activities were measured in the tissue samples. RESULTS: The IR group had considerably more hydropic degeneration, sinusoidal dilatation, and parenchymal mononuclear cell infiltration than the IRD, CeO2-IR, and CeO2-IRD groups. Catalase and GST enzyme activity were significantly higher in the CeO2-IR group than in the IR group. The MDA levels were found to be significantly lower in the IRD, CeO2-IR, and CeO2-IRD groups than in the IR group. CONCLUSION: Intraperitoneal CeO2 with desflurane reduced oxidative stress and corrected liver damage.

Hemodynamic responses to 1 MAC desflurane inhalation during anesthesia induction with propofol bolus and remifentanil continuous infusion: a prospective randomized single-blind clinical investigation.

BACKGROUND: Desflurane is not recommended during anesthesia induction because of its sympathetic stimulation effect, particularly in patients with myocardial ischemic disease. To date, the hemodynamic response to 1 MAC desflurane inhalation in combination with remifentanil infusion during anesthesia induction has rarely been reported. METHODS: This investigation was designed to compare hemodynamic responses to 1 MAC desflurane (group D, n = 200) with sevoflurane (group S, n = 200) during anesthesia induction and endotracheal intubation in adult patients undergoing elective spine surgery. Subgroup analysis of the different age subgroups was also performed. With continuous infusion of remifentanil 0.1 µg/kg/min, anesthesia was induced with propofol bolus, and endotracheal intubation was performed after muscle relaxation. Heart rate (HR) and mean arterial blood pressure (MAP) were measured every minute for 5 min after anesthesia induction (T1-5) and after endotracheal intubation (T6-10). RESULTS: HR was significantly higher in group D (n = 182) than in group S (n = 173) at T3-10 except at T6 (1 min after intubation) (all P < 0.05). In the age-based subgroup analyses, which subdivided the group D and S into four subgroups based on patient's age, the changes in HR from baseline values were significantly different between the coeval subgroups of patients in their 20-29 years and 30-39 years of age (all P < 0.05). MAP was reduced from baseline value, irrespective of group and age. CONCLUSION: Inhalation of 1 MAC desflurane during anesthesia induction with propofol bolus and remifentanil continuous infusion and during endotracheal intubation was more likely to induce elevations in HR more likely than 1 MAC sevoflurane, especially in younger patients. TRIAL REGISTRATION: This study was registered in the Clinical Research Information Service (CRIS, http://cris.nih.go.kr ) of the Republic of Korea on Feb 12, 2016 (Registration No. KCT 0,001,813).

Comparison of Antinociceptive Properties Between Sevoflurane and Desflurane Using Pupillary Dilation Reflex Under Equivalent Minimum Alveolar Concentration: A Randomized Controlled Trial.

BACKGROUND: The pupillary dilation reflex (PDR), the change in pupil size after a nociceptive stimulus, has been used to assess antinociception during anesthesia. The aim of this study was to compare the antinociceptive properties of sevoflurane and desflurane by measuring the PDR amplitude. METHODS: Seventy patients between 20 and 55 years of age were randomly allocated to receive either sevoflurane or desflurane. The PDR amplitude after an electrical standardized noxious stimulation (SNT) was measured using an infrared pupillometer under 1.0 minimum alveolar concentration (MAC). The pupil diameter was measured from 5 seconds before to 5 minutes after the SNT. The mean arterial pressure (MAP), heart rate (HR), and bispectral index (BIS) were also measured immediately before and after SNT as well as 1 minute and 5 minutes after SNT. The primary outcome was the maximum percent increase from the prestimulation value of the pupil diameter, and the secondary outcomes were the maximum percent increase from the prestimulation value of the MAP, HR, and BIS after SNT. RESULTS: The maximum percent increase of the pupil diameter after SNT was not different between the 2 groups (median [first quartile to third quartile], 45.1 [29.3-80.3] vs 43.4 [27.0-103.1]; median difference, -0.3 [95% confidence interval, -16.0 to 16.5]; P = .986). Before SNT, the MAP was higher under 1.0 MAC of sevoflurane than desflurane; however, the maximum percent increase of MAP, HR, and BIS was not different between the 2 groups. CONCLUSIONS: The amount of change in the PDR amplitude, MAP, and HR after SNT was not different between sevoflurane and desflurane anesthesia. This result might suggest that sevoflurane and desflurane may not have different antinociceptive properties at equivalent MAC.

Effect of combined intraoperative use of the Nociception Level (NOL) and bispectral (BIS) indexes on desflurane administration.

BACKGROUND: Currently, nociception monitors are not part of standard anaesthesia care. We investigated whether combined intraoperative nociception (NOL index) and anaesthesia (BIS index) monitoring during general anaesthesia would reduce anaesthetics consumption and enhance intraoperative safety and postoperative recovery when compared to standard of care monitoring (SOC). METHODS: In this randomised study, we included 60 patients undergoing colonic surgery under desflurane/remifentanil anaesthesia and epidural analgesia. Patients received either standard monitoring or combined BIS + NOL index monitoring. In the monitored group, remifentanil infusion was titrated to achieve a NOL index below 20. Desflurane was adjusted to BIS values (45-55). In the SOC group, remifentanil and desflurane were titrated on vital signs and MAC. The primary outcome was intraoperative desflurane consumption. RESULTS: Fifty-five patients were analysed. Desflurane administration was reduced in the monitored group from 0.25 ± 0.05 to 0.20 ± 0.06 mL kg-1 h-1 (p < 0.001). The cumulative time with a BIS under 40 was significantly higher in the SOC group with a median time of 12.6 min (95% CI: 0.6-80.0) versus 2.0 min (95% CI: 0.3-5.83) (p = 0.023). Time for extubation was significantly shorter in the monitored group: 4.4 min (95% CI: 2.4-4.9) versus 6.28 min (95% IC: 5.0-8.2) (p = 0.003). We observed no differences in remifentanil or phenylephrine requirements during anaesthesia or in postoperative outcome measures, such as postoperative pain, opioid consumption, neurocognitive recovery. CONCLUSION: Combined intraoperative monitoring of anaesthesia and nociception during colonic surgery resulted in less desflurane consumption and quicker extubation time compared to standard clinical care monitoring.

Influence of hemorrhage and subsequent fluid resuscitation on transcranial motor-evoked potentials under desflurane anesthesia in a swine model.

PURPOSE: Hemorrhage increases the effect of propofol and could contribute to false-positive transcranial motor-evoked potential (TcMEP) responses under total intravenous anesthesia (TIVA). We investigated the influence of hemorrhage and subsequent fluid resuscitation on TcMEPs under desflurane anesthesia. METHODS: Sixteen swine (25.4 ± 0.4 kg) were anesthetized with a 4% end-tidal desflurane concentration (EtDes), which was incrementally increased to 6%, 8%, and 10% and then returned to 4% every 15 min. This procedure was repeated twice (baseline). After baseline measurements, animals were allocated to either the hemorrhage (n = 12) or control (n = 4) group. In the hemorrhage group, 600 ml of blood was removed and the EtDes protocol described above was applied. Hypovolemia was resuscitated using 600 ml of hydroxyethyl starch and the EtDes protocol was applied again. TcMEPs were measured at each EtDes. In the control group, measurements were performed without hemorrhage or fluid infusion. RESULTS: TcMEP responses were observed in all conditions in all limbs with 4% EtDes (0.4 MAC). TcMEP amplitudes decreased according to the EtDes to a greater degree in the lower limbs compared with the upper limbs. Hemorrhage enhanced the effect of desflurane on TcMEP amplitudes, and decreased TcMEP by 41 ± 12% in upper limbs and 63 ± 17% in lower limbs compared with baseline. Subsequent fluid resuscitation did not reverse TcMEP amplitudes. CONCLUSIONS: TcMEP amplitudes decrease during hemorrhage under desflurane anesthesia. This phenomenon might result from an enhanced effect of desflurane on the spinal motor pathway without increasing the desflurane concentration.

Effect of desflurane on changes in regional cerebral oxygenation in patients undergoing one-lung ventilation is equivalent to the effect of propofol.

OBJECTIVES: Desaturation is an important clinical problem during one-lung ventilation (OLV) since it may induce cerebral hypoxia. Measurement of cerebral oxygenation has been shown to provide accurate information about episodes of cerebral hypoxemia. The purpose of this study was to compare the effect of desflurane on changes in cerebral oxygenation during OLV with the effect of propofol. METHODS: A randomized, single-blinded, prospective study was conducted. Fifty adult patients who were scheduled to undergo thoracic surgery were randomly assigned to anesthetic management using desflurane with remifentanil (Group D: n = 25) or using propofol and remifentanil (Group P: n = 25). RESULTS: The characteristics of the patients were very similar. Intergroup analysis of changes in cerebral oxygenation showed no significant difference on the operative side (two-way ANOVA, F (7, 368) = 0.425, p = 0.887) or the non-operative side (two-way ANOVA, F (7, 367) = 1.342, p = 0.229). Intragroup analysis of changes in cerebral oxygenation using one-way ANOVA showed no significant difference on the operative side (Group P; p = 0.585, Group D; p = 0.928) or the non-operative side in both groups (Group P; p = 0.657, Group D; p = 0.602). CONCLUSIONS: The effects of desflurane and propofol on changes in cerebral oxygenation in patients undergoing OLV were equivalent. Our results indicated that desflurane might be an appropriate anesthetic during OLV for maintaining cerebral oxygenation with an effective equivalent to that of propofol.

Molecular Mechanism of Gas Anesthetics on the Invasion, Metastasis, and Chemosensitivity of Osteosarcoma Cells.

BACKGROUND: Osteosarcoma is one of the most prominent bone cancers which has a predominant occurrence in children and adolescents. This study is focused on determining the effects of treatment of gas anesthetics on invasion, metastasis, and chemosensitivity in the progression of osteosarcoma cells. Material and Methods. The biological effects of the common gas anesthetics-desflurane, isoflurane, and sevoflurane-on osteosarcoma cells were studied and compared. The biological assays were performed for analysis of cell migration and proliferation. RESULTS: Isoflurane and sevoflurane have shown significant inhibition in the osteosarcoma cells at clinically relevant concentrations. Desflurane has shown less potent action on cell migration and inhibition. All three gas anesthetics have shown inhibition in cell proliferation. The effective antiproliferative action was at a clinically significant dose. At low millimolar concentrations, cell apoptosis was moderately affected. Drug combination analysis with chemotherapeutic drugs showed relevant inhibition in cell migration. All three agents showed significant augmentation of chemotherapeutic drugs in suppression and inhibition of inducing apoptosis. The antimigration action is likely to affect the PI3K/AKT pathway and IGF-1. CONCLUSION: The study demonstrates the proposed mechanisms of gas anesthetics and their differential effects on osteosarcoma cells and their survival, migration, growth, and chemosensitivity.

Effects of desflurane and sevoflurane on somatosensory-evoked and motor-evoked potential monitoring during neurosurgery: a randomized controlled trial.

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 < 0.05). The SEP latencies of both the upper and lower limbs in the desflurane group were significantly longer, and the SEP amplitudes were significantly lower than those in the sevoflurane group (P < 0.05). The MEP amplitudes in the desflurane group were significantly lower than those in the sevoflurane group (P < 0.05), only the amplitudes of the upper limbs at 0.3 MAC did not vary significantly. 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).

Activation of Orexinergic Neurons Inhibits the Anesthetic Effect of Desflurane on Consciousness State via Paraventricular Thalamic Nucleus in Rats.

BACKGROUND: Orexin, a neuropeptide derived from the perifornical area of the hypothalamus (PeFLH), promotes the recovery of propofol, isoflurane, and sevoflurane anesthesias, without influencing the induction time. However, whether the orexinergic system also plays a similar role in desflurane anesthesia, which is widely applied in clinical practice owing to its most rapid onset and offset time among all volatile anesthetics, has not yet been studied. In the present study, we explored the effect of the orexinergic system on the consciousness state induced by desflurane anesthesia. METHODS: The c-Fos staining was used to observe the activity changes of orexinergic neurons in the PeFLH and their efferent projection regions under desflurane anesthesia. Chemogenetic and optogenetic techniques were applied to compare the effect of PeFLH orexinergic neurons on the induction, emergence, and maintenance states between desflurane and isoflurane anesthesias. Orexinergic terminals in the paraventricular thalamic nucleus (PVT) were manipulated with pharmacologic, chemogenetic, and optogenetic techniques to assess the effect of orexinergic circuitry on desflurane anesthesia. RESULTS: Desflurane anesthesia inhibited the activity of orexinergic neurons in the PeFLH, as well as the neuronal activity in PVT, basal forebrain, dorsal raphe nucleus, and ventral tegmental area, as demonstrated by c-Fos staining. Activation of PeFLH orexinergic neurons prolonged the induction time and accelerated emergence from desflurane anesthesia but only influenced the emergence in isoflurane anesthesia, as demonstrated by chemogenetic and pharmacologic techniques. Meanwhile, optical activation of orexinergic neurons exhibited a long-lasting inhibitory effect on burst-suppression ratio (BSR) under desflurane anesthesia, and the effect may be contributed by the orexinergic PeFLH-PVT circuitry. The orexin-2 receptor (OX2R), but not orexin-1 receptor (OX1R), in the PVT, which had been inhibited most significantly by desflurane, mediated the proemergence effect of desflurane anesthesia. CONCLUSIONS: We discovered, for the first time, that orexinergic neurons in the PeFLH could not only influence the maintenance and emergence from isoflurane and desflurane anesthesias but also affect the induction under desflurane anesthesia. Furthermore, this specific effect is probably mediated by orexinergic PeFLH-PVT circuitry, especially OX2Rs in the PVT.

Sevoflurane and Desflurane Exposure Enhanced Cell Proliferation and Migration in Ovarian Cancer Cells via miR-210 and miR-138 Downregulation.

Inhalational anaesthetics were previously reported to promote ovarian cancer malignancy, but underlying mechanisms remain unclear. The present study aims to investigate the role of sevoflurane- or desflurane-induced microRNA (miRNA) changes on ovarian cancer cell behaviour. The cultured SKOV3 cells were exposed to 3.6% sevoflurane or 10.3% desflurane for 2 h. Expression of miR-138, -210 and -335 was determined with qRT-PCR. Cell proliferation and migration were assessed with wound healing assay, Ki67 staining and Cell Counting Kit-8 (CCK8) assay with or without mimic miR-138/-210 transfections. The miRNA downstream effector, hypoxia inducible factor-1α (HIF-1α), was also analysed with immunofluorescent staining. Sevoflurane or desflurane exposure to cancer cells enhanced their proliferation and migration. miR-138 expression was suppressed by both sevoflurane and desflurane, while miR-210 expression was suppressed only by sevoflurane. miR-335 expression was not changed by either sevoflurane or desflurane exposure. The administration of mimic miR-138 or -210 reduced the promoting effects of sevoflurane and desflurane on cancer cell proliferation and migration, in line with the HIF-1α expression changes. These data indicated that inhalational agents sevoflurane and desflurane enhanced ovarian cancer cell malignancy via miRNA deactivation and HIF-1α. The translational value of this work needs further study.

Cognitive status of patients judged fit for discharge from the post-anaesthesia care unit after general anaesthesia: a randomized comparison between desflurane and propofol.

BACKGROUND: The Aldrete's score is used to determine when a patient can safely leave the Post-Anaesthesia Care Unit (PACU) and be transferred to the surgical ward. The Aldrete score is based on the evaluation of vital signs and consciousness. Cognitive functions according to the anaesthetic strategy at the time the patient is judged fit for discharge from the PACU (Aldrete's score ≥ 9) have not been previously studied. The aim of this trial was to assess the cognitive status of inpatients emerging either from desflurane or propofol anaesthesia, at the time of PACU discharge (Aldrete score ≥ 9). METHODS: Sixty adult patients scheduled for hip or knee arthroplasty under general anaesthesia were randomly allocated to receive either desflurane or propofol anaesthesia. Patients were evaluated the day before surgery using Digit Symbol Substitution Test (DSST), Stroop Color Test and Verbal Learning Test. After surgery, the Aldrete score was checked every 5 min until reaching a score ≥ 9. At this time, the same battery of cognitive tests was applied. Each test was evaluated separately. Cognitive status was reported using a combined Z score pooling together the results of all 3 cognitive tests. RESULTS: Among the 3 tests, only DSST was significantly reduced at Aldrete Score ≥ 9 in the Desflurane group. Combined Z-scores at Aldrete Score ≥ 9 were (in medians [interquartils]): - 0.2 [- 1.2;+ 0.6] and - 0.4 [- 1.1;+ 0.4] for desflurane and propofol groups respectively (P = 0.62). Cognitive dysfunction at Aldrete score ≥ 9 was observed in 3 patients in the Propofol group and in 2 patients in the Desflurane group) (P = 0.93). CONCLUSION: No difference was observed in cognitive status at Aldrete score ≥ 9 between desflurane and propofol anaesthesia. Although approximately 10% of patients still had cognitive dysfunctions, an Aldrete score ≥ 9 was associated with satisfactory cognitive function recovery in the majority of the patients after lower limb arthroplasty surgery under general anaesthesia. TRIAL REGISTRATION: Clinical Trials identifier NTC02036736 .

Remifentanil infusion during desflurane anesthesia reduces tissue blood flow while maintaining blood pressure and tissue oxygen tension in the masseter muscle and mandibular bone marrow.

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.

Mechanistic consideration of the effect of perioperative volatile anesthetics on phagocytes.

A growing literature has shown that volatile anesthetics are promiscuous molecules targeting multiple molecules, some of which are critical for immunological functions. We focused on studies that delineated target molecules of volatile anesthetics on immune cells and summarized the effects of volatile anesthetics on immune functions. We also presented the perspectives of studying volatile anesthetics-mediated immunomodulation.

State-Dependent Cortical Unit Activity Reflects Dynamic Brain State Transitions in Anesthesia.

Understanding the effects of anesthesia on cortical neuronal spiking and information transfer could help illuminate the neuronal basis of the conscious state. Recent investigations suggest that the brain state identified by local field potential spectrum is not stationary but changes spontaneously at a fixed level of anesthetic concentration. How cortical unit activity changes with dynamically transitioning brain states under anesthesia is unclear. Extracellular unit activity was measured with 64-channel silicon microelectrode arrays in cortical layers 5/6 of the primary visual cortex of chronically instrumented, freely moving male rats (n = 7) during stepwise reduction of the anesthetic desflurane (6%, 4%, 2%, and 0%). Unsupervised machine learning applied to multiunit spike patterns revealed five distinct brain states. A novel desynchronized brain state with increased spike rate variability, sample entropy, and EMG activity occurred in 6% desflurane with 40.0% frequency. The other four brain states reflected graded levels of anesthesia. As anesthesia deepened the spike rate of neurons decreased regardless of their spike rate profile at baseline conscious state. Actively firing neurons with wide-spiking pattern showed increased bursting activity along with increased spike timing variability, unit-to-population correlation, and unit-to-unit transfer entropy, despite the overall decrease in transfer entropy. The narrow-spiking neurons showed similar changes but to a lesser degree. These results suggest that (1) anesthetic effect on spike rate is distinct from sleep, (2) synchronously fragmented spiking pattern is a signature of anesthetic-induced unconsciousness, and (3) the paradoxical, desynchronized brain state in deep anesthesia contends the generally presumed monotonic, dose-dependent anesthetic effect on the brain.SIGNIFICANCE STATEMENT Recent studies suggest that spontaneous changes in brain state occur under anesthesia. However, the spiking behavior of cortical neurons associated with such state changes has not been investigated. We found that local brain states defined by multiunit activity had a nonunitary relationship with the current anesthetic level. A paradoxical brain state displaying asynchronous firing pattern and high EMG activity was found unexpectedly in deep anesthesia. In contrast, the synchronous fragmentation of neuronal spiking appeared to be a robust signature of the state of anesthesia. The findings challenge the assumption of monotonic, anesthetic dose-dependent behavior of cortical neuron populations. They enhance the interpretation of neuroscientific data obtained under anesthesia and the understanding of the neuronal basis of anesthetic-induced state of unconsciousness.

Desflurane anesthesia shifts the circadian rhythm phase depending on the time of day of anesthesia.

Desflurane is one of the most frequently used inhalational anesthetics in clinical practice. A circadian rhythm phase-shift after general anesthesia with sevoflurane or isoflurane has been reported in mice, but few studies have reported this effect with desflurane. In the present study, we examined the rest/activity rhythm of mice by counting the number of running wheel rotations, and we found that desflurane anesthesia caused a phase shift in the circadian rhythm that was dependent on the time of day of anesthesia. We also found that desflurane anesthesia altered the relative mRNA expression of four major clock genes (Per2, Bmal, Clock, and Cry1) in the suprachiasmatic nucleus (SCN). These results are important for elucidating the effects of desflurane on the SCN, which is the master clock for the mammalian circadian rhythm. Further studies on the relationship between anesthesia and circadian rhythm may lead to the prevention and treatment of postoperative complications related to circadian rhythms.

Comparison of vasodilatory properties between desflurane and sevoflurane using perfusion index: a randomised controlled trial.

BACKGROUND: 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. METHODS: 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. RESULTS: 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; P<0.001) and after tetanic stimulation (MD: 2.8; 95% CI: 2.0-3.7; P<0.001). Higher PI paralleled lower MAP in participants assigned to desflurane anaesthesia (P<0.001), 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. CONCLUSIONS: These findings suggest that at equipotent doses, desflurane exerts more potent vasodilatory properties and lowers blood pressure by a magnitude potentially associated with harm. CLINICAL TRIAL REGISTRATION: NCT03570164.

Desflurane Preconditioning Protects Against Renal Ischemia-Reperfusion Injury and Inhibits Inflammation and Oxidative Stress in Rats Through Regulating the Nrf2-Keap1-ARE Signaling Pathway.

OBJECTIVE: Kidney is sensitive to ischemia-reperfusion (I/R) injury because of its special structure and function. In this study, we aimed to explore the mechanism of desflurane (DFE) preconditioning effecting on renal I/R injury in rats. METHODS: Renal I/R injury rats model was constructed, and the expressions of serum renal function parameters (blood urea nitrogen (BUN) and serum creatinine (SCr)) and lipid peroxidation-related factors were detected using corresponding commercial kits to assess the degrees of renal functional damage and oxidative stress. Hematoxylin--eosin (HE) staining and Masson trichrome staining were applied to measure the renal histologic damage. The expressions of inflammation-related factors were determined by ELISA assay. The cell apoptosis was analyzed using TUNEL, Western blot and immunohistochemistry (IHC). IHC was also used to detect the number of myeloperoxidase (MPO)-positive cells. The expressions of proteins associated with the Nrf2-Keap1-ARE pathway were assessed by Western blot and IHC. RESULTS: DFE preconditioning inhibited I/R injury-induced BUN and SCr increase and renal histologic injury in rats. Also, DFE suppressed the inflammation, apoptosis and oxidative stress caused by renal I/R injury in vivo. In addition, DFE preconditioning repressed peroxide-related factors (MDA, MPO and NO) expressions and promoted antioxidant-related factors (GSH, SOD, GPx and CAT) expressions. In addition, DFE promoted Nrf2-Keap1-ARE-related proteins including Nrf2, NQO1, HO-1, γ-GCS, GSR and GCLc expressions. CONCLUSION: DFE preconditioning protected the kidney as well as inhibited the inflammation, cell apoptosis and oxidative stress in renal I/R injury rats by activating the Nrf2-Keap1-ARE signaling pathway.